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HX64130614 
RC663  .H46  Scurvy,  past  and  | 


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SCURVY 

PAST  AND  PRESENT 


BY 

ALFRED  F.  HESS,  M.D. 

CLINICAL    PROFESSOR    OF    PEDIATRICS,    UNIVERSITY   AND    BELLEVUE    HOSPITAL 
MEDICAL    COLLEGE,    NEW    YORK   CITY 


ILLUSTRATED 


PHILADELPHIA  AND  LONDON 
J.  B.  LIPPINCOTT   COMPANY 


COPYRIGHT,    IQ20,   BY  J.    B.    LIPPINCOTT   COMPANY 


PRINTED    BY   J.    B.   LIPPINCOTT  COMPANY 
AT  THE  WASHINGTON  SQUARE  PRESS 
PHILADELPHIA,    U.S.A. 


PREFACE 

Interest  in  scurvy  has  been  stimulated  in  the  last 
few  years  as  the  result  of  a  new  and  broader  conception 
of  nutrition.  It  has  come  to  be  realized  that  in  addition 
to  the  substances  heretofore  recognized  as  of  essential 
importance  in  the  dietary — the  proteins,  fats,  carbohy- 
drates and  the  salts — there  is  still  another  group,  termed 
"vitamines,"  "accessory  food  factors"  or  "food  hor- 
mones/'  which  must  be  included  in  order  to  render  the 
diet  complete  and  adequate.  It  has  become  increasingly 
evident  that  the  attention  of  physiologists  and  of  clinicians 
has  been  focussed  too  sharply  and  too  narrowly  on  the 
caloric  value  of  foodstuffs.  At  the  same  time  we  have 
begun  to  appreciate  the  existence  of  a  group  of  nutritional 
disorders  which  depend  largely  on  a  deficiency  of  these 
illusive  vitamines  or  food  factors,  and  which  evidently 
are  of  vital  importance  to  the  welfare  of  the  individual 
and  of  mankind.  Scurvy  is  one  of  this  newly-constituted 
group,  and  due  to  this  association  has  acquired  a  fresh 
and  broader  significance.  It  is  in  this  light  that  the  inten- 
sive research  work  must  be  interpreted,  which  has  been 
applied  within  the  past  few  years,  both  in  this  country 
and  abroad,  to  problems  relating  to  this  disorder.  It  is 
clear  that  the  subject  is  in  its  infancy,  and  is  destined  to 
participate  in  a  consideration  of  many  of  the  nutritional 
and  infectious  diseases  of  the  adult  and  the  child. 

The  World  War  has  tended  also  to  demand  a  renewed 
consideration  of  scurvy.  This  disorder  has  played  a  role 
in  all  wars — in  the  campaigns  of  the  Caesars,  the  pilgrim- 
ages of  the  Crusaders,  and  the  numerous  wars  of  the  last 
century.    In  the  recent  war  it  existed  among  the  various 

iii 


iv  PREFACE 

armies,. particularly  those  in  the  East,  to  an  extent  greater 
than  at  first  was  realized.  In  Mesopotamia  it  is  stated  to 
have  been  one  of.  the  decisive  factors  in  forcing  the  sur- 
render of  the  British  at  Kut.  Its  incidence,  however,  was 
not  limited  to  the  military  forces.  Eeports  from  England 
and  the  continental  countries  clearly  indicate  that  scurvy 
prevailed  among  the  civilian  population  during  the  past 
few  years  to  a  degree  unknown  in  peace  times.  This  was 
especially  true  of  infants  and  children. 

For  the  past  seven  years  I  have  been  engaged  in  an 
investigation  of  scurvy  both  in  the  laboratory  and  in 
the  clinic,  and  have  treated  various  aspects  of  the  subject 
in  a  large  number  of  articles  published  in  various  medical 
journals.  In  the  course  of  these  studies  there  has  been 
ample  opportunity  for  a  comprehensive  review  of  the 
widely-scattered  literature.  No  treatise  on  scurvy  has 
been  published  in  English  since  the  classical  work  of 
Lind  in  1772.  The  time,  therefore,  seemed  opportune  to 
gather  into  one  volume  the  recent  advances  in  this  field 
and  to  offer  to  the  clinician,  to  the  hygienist,  and  to  the 
biological  chemist  a  presentation  of  the  existing  status 
of  this  important  nutritional  disease. 

It  is  with  pleasure  that  I  acknowledge  my  obligation 
to  Dr.  Lester  J.  Unger,  who  has  assisted  in  carrying  out 
much  of  the  work  described  in  this  volume.  Thanks  are 
due  also  to  Dr.  Charles  Gottlieb  for  the  radiographs  which 
are  here  reproduced,  and  to  Dr.  Gertrude  McCann  for 
seeing  the  work  through  the  press.  To  my  associates  in 
the  clinic  who  shared  in  the  observations,  and  to  friends 
who  read  various  chapters  in  the  course  of  their  prepara- 
tion, I  wish  to  express  my  appreciation. 

Alfeed  F.  Hess. 

New  York, 

August,  1920. 


CONTENTS 


PAGE 

Preface.  iii-iv 

CHAPTER  I 

History  of  Scurvy 1 

(a)  Outbreaks  on  Land  ;  (b)  Outbreaks  at  Sea  ;  (c)  Infantile 
Scurvy  ;  (d)  Scurvy  in  the  World  War 

CHAPTER  II 

Pathogenesis  and  Etiology 23 

Pathogenesis  :  Theories  ;  Potassium  Deficiency  ;  Acidosis  ; 
Toxic  ;  Bacterial  ;  Vitamine  (Accessory  Factor) 

Etiology  :  Breast  Fed  Infants 35 

Artificially  Fed  Infants  :  Pasteurized  Milk  ;  Boiled  and  Ster- 
ilized Milk  ;  Dried  Milk  ;  Condensed  Milk  ;  Proprietary 

Foods  (Effect  of  Alkalization) 40 

Age,  Season  and  Climate  ;  Economic  Status  ;  Psychic  Element  ; 
Predisposition  ;  Effect  of  Other  Food  Constituents  ;  Ex- 
citing Factors 

CHAPTER  III 
The  Antiscorbutic  Vitamine 62 

Characteristics  :  Relation  to  Heat,  Drying,  Aging,  Ultra- 
violet Rays,  Shaking 65 

Mode  of  Action — (a)  Direct  :  As  a  Nutriment  ;  Antitoxin  ;  Cat- 
alyzer ;   (6)  Indirect  :  Endocrine  Action 69 

Fate  in  the  Body  :  Storing  ;  Content  in  Blood  ;  Excretion  ; 
Fate  in  Gastro-intestinal  Tract;  Effect  on  Digestive 
Processes 74 

Irregularities  of  Action  ;  Effect  on  Growth 

CHAPTER  IV 
Pathology 81 

(a)  Gross  :  General  Appearance  ;  Hemorrhages  ;  Anasarca  ; 
Heart  ;  Lungs  ;  Alimentary  Tract  and  its  Glands  ;  Urinary 
Tract  ;  Lymph  Nodes  ;  Organs  of  Internal  Secretion  ; 
Brain  and  Spinal  Cord  ;  Bones;  (6)  Microscopic  :  Skin  ; 
Muscles  ;  Blood-vessels  ;  Lungs  ;  Heart  ;  Intestinal  Tract 
and  its  Glands  ;  Kidney  ;  Adrenals  ;  Pancreas  ;  Thymus  ; 
Central  Nervous  System  ;  Peripheral  Nerves  ;  Retina  ; 
Bones 

CHAPTER  V 

Experimental  Scurvy Ill 

Historical  Review 

Pathogenesis 116 

Pathology  :  Effect  on  the  Fcetus  ;  Scurvy  in  the  Monkey; 
Microscopic  Pathology  ;  Bones  ;   Teeth  ;    Nerves  ;   Blood 

Vessels  ;  Interpretation  of  Bacteria  in  the  Tissues 122 

Symptoms 135 

T 


vi  CONTENTS 

CHAPTER  VI 

Antiscorbutic  Foods 143 

Historical  Review 143 

Milk  :  Raw  ;  Pasteurized  ;  Dried 150 

Fruits  and  Fruit  Juices  :  Dried  153 

Vegetables:  Cabbage;  Effect  of  Heating.    Potato.   Swede 158 

Dehydrated  Vegetables;  Canned  Foods  (Tomatoes) 166 

Germinated  Cereals  and  Pulses  ;    Meat  and  Eggs  ;   Beer  and 

Alcoholic  Beverages  ;  Miscellaneous 
Conclusions 173 

CHAPTER  Vn 

Symptomatology  and  Diagnosis 176 

In  Adults 176 

In  Infants  :  (a)  Acute  ;  (6)  Subacute  ;  (c)  Latent. — Hemorrhage 
of  Gums  ;  Subperiosteal  Hemorrhage:  Skin  ;  Mucous  Mem- 
branes and  Subcutaneous  Tissues  ;  Hemorrhages  of  In- 
ternal Organs  ;  Nails  and  Hair;  Eczema  ;  Edema;  Tender- 
ness ;  Beading  of  Ribs;  Separation  of  Epiphysis  ;  "  White 
Line";  Cardiovascular  System;  "Cardiorespiratory  Syn- 
drome ";  Nervous  System  ;  Urinary  System  ;  the  Blood  and 
Blood-vessels  ;  Nutrition  and  Growth  ;  Fever  ;  Complica- 
tions; Epidemic  Form 183 

Differential     Diagnosis  :    Rheumatism  ;     Purpura  ;     Congenital 

Syphilis;  Bone  Tumors  ;  Osteomyelitis;  Poliomyelitis,  etc.  . .  219 

CHAPTER  VIII 
Prognosis 225 

CHAPTER  IX 
Treatment 230 


Preventive  ;  Curative 
Non-dietetic 


CHAPTER  X 


Metabolism 241 

In  Adults:   Body  Exchanges 241 

In  Infants:    Body  Exchanges  ;  Analysis  of  Organs  ;  Chemistry 

of  Blood 242 

In  Animals:  Monkey;  Guinea-Pig 245 

CHAPTER  XI 

Relation  of  Scurvy  to  Other  Diseases 248 

Beriberi  ;  Ship-beriberi  ;  Pellagra  ;  Rickets  ;  Osteogenesis 
Imperfecta;  Osteomalacia;  Hunger  Edema;  "  Mehlnaerscha- 
den  ";  Exudative  Diathesis  ;   Diseases  Due  to  a  Food  Excess 

Appendix  :    Lind's  Precipes  for  Preparing  Stable  Antiscorbutics.  .  259 

Bibliography 261 


ILLUSTRATIONS 

FIG.  PAGE 

1.  Dependence  on  potato  as  antiscorbutic 7 

2.  Weight  curve  of  scorbutic  baby.     Effect  of  alkalization  of  milk ....  51 

3.  Lumbar  cord  in  case  of  scurvy 104 

4.  Lumbar  cord  in  case  of  scurvy.     Focal  degeneration 104 

5.  Bone  in  scurvy.     Microscopic  pathology 105 

6.  Subperiosteal  hemorrhage  and  separation  of  epiphysis.    Roentgeno- 

gram    108 

7.  Complete  restitution  of  epiphysis  without  deformity.     Roentgeno- 

gram    109 

8.  Curve  of  fecal  excretion  in  scurvy 120 

9.  Diagrammatic  representation  of  guinea-pig  scurvy 128 

10.  Loss  of  weight  in  guinea-pig  scurvy 139 

11.  Dried  milk  as  an  antiscorbutic 140 

12.  Dehydrated  vegetables  as  a  cause  of  scurvy 164 

13.  Cure  of  scurvy  by  addition  of  canned  tomato 166 

14.  Failure  of  yeast  as  prophylactic 171 

15.  Temperature,  pulse,  and  respiration  in  scurvy 186 

16.  Subperiosteal  hemorrhage  and  separation  of  epiphysis.    Roentgeno- 

gram    192 

17.  Periosteal  "tags"  and  "streamers."     Roentgenogram 193 

18.  Infant  with  marked  scurvy.     Characteristic  position 198 

19.  Scorbutic  beading  of  ribs.     Roentgenogram 198 

20.  "White  line."     Roentgenogram 199 

21.  Cardiac  enlargement.     Roentgenogram 200 

22.  Electrocardiogram  showing  "cardiorespiratory  syndrome" 201 

23.  Stationary  weight  during  cure  of  scurvy.     Oliguria  followed  by 

polyuria 206 

24.  Development  of  scurvy  in  spite  of  normal  gain  in  weight 214 

25.  Retardation  of  growth  in  length  when  no  orange  juice  was  given 

and  supergrowth  when  given  once  more 216 

TABLES 

TABLE  PAGE 

1.  Fecal  flora  of  scorbutic  infants 29 

2.  Necropsy  reports  of  scurvy 82 

3.  Relative  distribution  of  the  antiscorbutic  factor  in  the  commoner 

food  stuffs 157 

4.  Platelets  and  other  blood  cells  in  scurvy 209 

5.  Data  of  epidemic  of  scurvy 218 

6.  Duration  of  treatment  before  marked  improvement  was  noticed. . .  237 

vii 


SCURVY 

PAST  AND   PRESENT 

CHAPTER  I 
HISTORY  OF  SCURVY  * 

Outbreaks  on  Land.-— Like  many  other  diseases,  the  life 
history  of  scurvy  shows  several  distinct  phases.  We  hear 
of  it  first  as  a  plague,  infesting  armies  and  besieged 
towns;  then  as  a  dread  disease,  decimating  the  sailors 
of  the  navy  and  of  the  mercantile  marine,  and,  since  the 
end  of  the  last  century,  more  often  as  a  nutritional  dis- 
turbance, endangering  the  health  of  infants.  Very  re- 
cently it  has  acquired  an  entirely  new  interest,  as  the 
representative  of  a  class  of  disorders  which  has  re- 
vealed the  essential  importance  to  man  of  unknown 
dietary  factors. 

It  is  difficult,  as  may  be  imagined,  to  define  with  pre- 
cision the  earliest  description  of  scurvy,  as  the  older 
references  are  so  vague  as  to  be  open  to  individual  inter- 
pretation. The  reference  of  Hippocrates  to  a  large  num- 
ber of  men  in  the  army  who  suffered  from  pains  in  the 
legs  and  gangrene  of  the  gums,  which  was  accompanied 
by  loss  of  teeth,  seems  sufficiently  definite  to  be  identified 
as  this  disease.  The  Greek,  Roman  and  Arabian  writers 
do  not  seem  to  have  been  acquainted  with  scurvy.  This 
is  as  we  should  expect,  for  fruits  and  vegetables  grew  in 

1  The  best  historical  review  of  scurvy  is  to  be  found  in  Hirach's  Hand- 
book of  Geographic  and  Historical  Pathology,  from  which  account  we  have 
drawn  many  facts. 

1 


2  SCURVY:    PAST  AND  PRESENT 

such  plenty  in  these  southern  countries  that  scurvy  must 
have  been  a  disorder  of  rare  occurrence. 

An  interesting  early  description  of  scurvy,  and  one 
which  is  quite  convincing,  is  that  of  de  Joinville,  who 
accompanied  the  Crusaders  in  their  invasion  of  Egypt 
under  St.  Lewis,  about  the  middle  of  the  thirteenth  cen- 
tury. He  refers  to  the  lividity  and  spongy  condition  of 
the  gums,  and  describes  how  "the  barber  surgeons  were 
forced  to  cut  away  the  dead  flesh  from  the  gums  to  enable 
the  people  to  masticate  their  food";  he  describes  their 
debility,  their  tendency  to  faint,  and  the  black  spots  on 
their  legs.  The  disease  broke  out  in  Lent,  during  which 
time  the  soldiers  partook  of  no  meat,  but  consumed  a 
species  of  eel  which  they  believed  ' '  ate  the  dead  people ' ' 
and  therefore  led  to  this  loathsome  disease. 

It  is  probable  that  scurvy  existed  in  the  northern  parts 
of  Europe  and  Asia  ever  since  they  were  settled  by  man. 
We  should  hardly  expect  to  have  records  of  this  condition, 
in  view  of  the  low  educational  status  of  the  people,  their 
greatly  restricted  literature,  and  their  lack  of  intercourse 
with  the  people  in  the  southern  countries.  In  the  sixteenth 
century,  with  the  development  and  spread  of  education, 
we  begin  to  hear  of  scurvy  from  various  sources.  Claus 
Magnus,  in  his  "History  of  the  Northern  Nations,' '  pub- 
lished in  1555,  described  the  disease  which  he  tells  us 
flourished  among  the  soldiers  in  the  camps  and  in  the 
prisons.  About  this  time  Ronsseus,  Echtius  and  Wierus 
wrote  special  treatises  on  this  disease,  and  recommended 
many  dietary  measures  which  we  recognize  to-day  as  most 
efficacious.  The  number  of  monographs  on  this  subject 
multiplied  with  great  rapidity  in  the  course  of  the  next 
twenty-five  or  fifty  years ;  none  of  them,  however,  added 
anything  essential  to  our  knowledge.    In  1645  the  Faculty 


HISTORY  OF  SCURVY  3 

of  Medicine  at  Copenhagen  published  a  "consilium"  for 
the  benefit  of  the  poor,  treating  of  the  causes,  prevention 
and  cure  of  this  disease,  which  was  prevalent  among  the 
Danes  and  other  northern  nations. 

The  colonists  of  the  northern  part  of  America  were 
sorely  afflicted  with  scurvy.  It  is  said  that  the  French 
met  with  such  high  mortality  during  the  severe  winters 
in  Canada,  that  they  frequently  debated  the  wisdom  of 
abandoning  this  settlement.  This  was  true  also  in  regard 
to  the  English  and  their  settlement  in  Newfoundland. 
Indeed,  it  was  scurvy  which  forced  the  early  settlers  in 
Hudson  Bay  to  discontinue  their  intentions  of  colonizing 
that  region. 

In  an  essay  published  in  the  eighteenth  century  (1734), 
Bachstrom  described  an  epidemic  of  scurvy  which 
occurred  in  1703  during  the  siege  of  Thorn,  in  Prussia, 
by  the  Swedes,  which  caused  the  death  of  5000  of  the  gar- 
rison, in  addition  to  a  large  number  of  the  inhabitants. 
It  is  interesting  to  note  that  this  epidemic  took  place  in 
the  middle  of  the  summer,  and  not  in  the  cold  season. 
From  this  time  on  we  meet  with  many  descriptions  of 
scurvy  in  connection  with  the  wars  at  various  periods. 
For  instance,  in  the  Russian  armies,  in  the  war  between 
the  Austrians  and  the  Turks  in  1720;  in  the  English 
troops  who  had  taken  Quebec  from  the  French  in  1759; 
among  the  French  soldiers  in  the  army  of  the  Alps  in  the 
spring  of  1795.  It  is  unnecessary  to  review  these  accounts 
in  detail.  This  period  is  distinguished  rather  by  the 
appearance  of  a  great  classic  on  Scurvy,  the  work  of  the 
English  naval  hygienist,  Lind  (1752).  This  book  has 
intrinsic  value  to-day,  and,  at  the  time  it  appeared,  served 
to  crystallize  the  conception  of  scurvy,  which  had  been 
stretched  out  of  all  proportions  to  include  an  ever-increas- 


4  SCURVY:    PAST  AND  PRESENT 

ing  conglomeration  of  clinical  conditions.  Scurvy  had 
become  the  Alpha  and  Omega  of  professional  routine, 
the  catchword  of  the  day,  the  asylum  ignorantiae  of  the 
practical  man.  Into  this  chaos,  as  Hirsch  expresses  it, 
"the  first  beams  of  light  fell  when  Lind's  classical 
work  appeared." 

It  will  be  of  little  value  to  consider  the  great  number 
of  epidemics  of  scurvy  which  occurred  from  this  time  to 
the  present  day.  They  may  be  found  in  tabular  form  in 
the  excellent  survey  of  scurvy  by  Hirsch.  The  literature 
of  this  long  period  may  likewise  be  found  in  a  work  of 
encyclopaedic  character,  that  of  Krebel,  which  gives  the 
titles,  with  a  summary  of  the  various  articles  on  this  sub- 
ject, appearing  to  the  year  1859.  If  we  look  over  the 
chronological  table  compiled  by  Hirsch,  we  note  a  remark- 
able similarity  regarding  the  incidence  of  the  recurring 
epidemics.  In  almost  all  cases  they  broke  out  among 
troops,  whether  in  Russia,  in  India,  in  Africa,  or  in  our 
United  States.  The  epidemics  which  are  not  attributable 
to  military  life  or  campaigns  are  found  to  have  taken 
place  generally  in  prisons,  insane  asylums,  poorhouses  or 
houses  of  refuge  and  correction.  It  would  seem  that  no 
war  is  omitted  from  this  list  of  sickness  and  death.  There 
are  in  all  143  land  epidemics  between  1556  and  1877,  two 
occurring  in  the  sixteenth  century,  four  in  the  seventeenth, 
33  in  the  eighteenth,  and  104  in  the  nineteenth  century. 
The  marked  increase  in  the  nineteenth  century  occurred 
in  institutions,  in  asylums  and  prisons,  rather  than  in  the 
armies.  This  fact  may  be  ascribed  to  altered  social  con- 
ditions which  led  to  a  great  multiplication  of  eleemosy- 
nary institutions. 

Coming  down  to  more  recent  times,  we  learn  that 
scurvy  occurred  extensively  during  the  Crimean  War,  and 


HISTORY  OF  SCURVY  5 

that  it  was  prevalent  also  among  the  troops  in  our  own 
Civil  War.  In  the  "Medical  and  Surgical  Histoiy  of  the 
War  of  the  Rebellion/ '  we  find  the  following  statements  : 

"A  scorbutic  tendency  was  developed  at  most  of  our 
military  posts  during  the  winter  season,  after  the  troops 
had  been  confined  to  the  use  of  the  ordinary  ration  with 
the  desiccated  vegetables.  The  latter  in  the  quantities 
failed  to  repress  the  disease.  At  posts  which  could  be 
readily  supplied  with  potatoes  only  the  taint  was  mani- 
fested, on  account  of  a  want  of  liberality  in  the  issues.' ' 
And  again:  "Among  the  white  troops  during  the  five  and 
one-sixth  years  covered  by  the  statistics,  30,714  cases  of 
scurvy  were  reported;  and  383  deaths  were  attributed 
directly  to  that  disease. ' ' 

Munson  writes:  "It  (scurvy)  prevailed  among  our 
troops  during  the  Civil  War  and  its  recognition  was  a 
surprise  and  shock  to  professional  ideas  preconceived 
from  practice  in  civil  life. '' 

As  is  well  known,  the  besieged  in  Paris  during  the 
Franco-Prussian  War  in  the  winter  of  1870-71  suffered 
severely  from  scurvy.  The  accounts  of  their  pitiable  con- 
dition have  been  portrayed  for  us  by  numerous  French 
writers  (Delpech,  Hayem,  Laseque  and  Legroux).  The 
people  lived  mainly  on  rice  and  bread,  with  an  occasional 
addition  of  potatoes  or  horse  meat.  The  winter  was  ex- 
ceptionally severe,  which  was  supposed  to  have  intensified 
the  scorbutic  condition.  Not  only  were  the  inmates  of  the 
prisons  on  the  Seine  attacked,  numbering  about  one  thou- 
sand, but  even  the  patients  in  the  military  hospitals  devel- 
oped the  disease.  It  is  of  interest  to  remember  that  the 
siege  lasted  but  little  over  four  months,  from  September 
17th  to  January  27th,  the  date  of  the  armistice. 


6  SCURVY:    PAST  AND  PRESENT 

In  the  Russo-Japanese  War,  after  the  siege  of  Port 
Arthur,  it  was  found  that  one-half  of  the  garrison  of 
17,000  men  had  scurvy. 

Although  there  are  certain  parts  of  the  world  where 
scurvy  is  of  frequent  occurrence,  no  country  has  been 
entirely  free  from  it.  As  might  be  expected,  it  has  been 
particularly  prevalent  in  the  North,  where  vegetation 
is  scanty — in  Greenland,  Alaska,  Russia  and  the  Baltic 
States.  It  has  likewise  prevailed  in  the  tropics  when 
the  crops  have  failed.  India  has  been  conspicuous  for  its 
large  number  of  epidemics;  some  years  ago  scurvy 
occurred  in  Arabia  among  the  English  troops  stationed 
at  Aden,  both  among  the  British  and  the  native  troops. 
A  recent  communication  from  Aruba,  a  small  island  of 
Dutch  Guiana,  lying  north  of  Venezuela,  illustrates  how 
devastating  scurvy  still  is  in  some  parts  of  the  world. 
This  account  tells  of  3000  cases  of  this  disease  which 
occurred  in  1915  among  a  population  of  less  than  10,000, 
owing  to  the  fact  that  the  crops  had  failed  almost  entirely 
during  the  years  1912, 1913  and  1914. 

It  is  important  for  us  to  realize  that  we  are  still  de- 
pendent on  the  annual  crops  for  our  protection  from 
scurvy;  in  other  words,  the  world  is  leading  a  hand-to- 
mouth  existence  in  regard  to  its  quota  of  antiscorbutic 
food.  The  truth  of  this  condition  has  been  realized  for 
Ireland,  sadly  illustrated  by  numerous  epidemics,  notably 
the  great  epidemic  of  1847  reported  by  Curran.  It  was 
demonstrated  by  the  outbreaks  of  scurvy  in  Norway  in 
1904  and  1912,  and  was  brought  to  the  attention  of  many 
in  the  United  States  in  the  spring  of  1916.  In  this  year 
our  potato  crop  fell  far  below  the  normal,  with  the  result 
that  scurvy  appeared  in  various  parts  of  the  United 
States,  especially  in  institutions  (Fig.  1). 


HISTORY  OF  SCURVY 


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Fig.  1. — A  comparison  between  the  requisitioned  quantity  (in  thousand  pound  units')  of 
potatoes  and  other  vegetables,  and  the  quantity  received  per  month  by  an  institution  in 
which  more  than  200  cases  of  scurvy  occurred  at  the  beginning  of  April,  1016.  The  total 
height  of  column  represents  the  amount  needed  and  requisitioned;  the  solid  black  portion 
the  amount  received.     The  number  of  inmates  in  the  institution  remained  approximately 

the  same. 
The  chart  illustrates  our  great  dependence  on  the  potato  during  the  winter  months.    This 
is  due  not  only  to  its  intrinsic  antiscorbutic  potency,  but,  probably  quite  as  much,  to  the 
fact  that  fully  twice  as  many  pounds  of  potatoes  are  consumed  during  the  winter  as  of  all 
other  vegetables  combined.    Therefore,  if  this  crop  fails  or  is  dehydrated,  scurvy  will  develop 

in  the  spring. 


8  SCURVY:    PAST  AND  PRESENT 

The  fact  that  scurvy  may  occur  in  any  land  and  cli- 
mate, even  in  the  garden  spots  of  the  world,  is  strikingly 
shown  by  the  epidemics  reported  from  Algiers,  and  the 
ravages  of  this  disease  among  the  gold  seekers  in  Califor- 
nia in  1849.  Nothing  could  be  more  incongruous  than  the 
occurrence  of  a  deficiency  disease  in  this  land  of  plenty. 

Outbreaks  at  Sea. — It  is  doubtful,  however,  whether 
attention  would  have  been  f  ocussed  so  early  and  so  sharply 
on  scurvy,  had  it  not  been  for  the  voyages  of  exploration 
undertaken  in  the  sixteenth  century.  These  long  trips 
on  sailing  vessels,  where  for  many  months  little  or  no  fresh 
vegetable  or  animal  food  was  obtainable,  were  almost  as 
if  designed  to  make  a  test  of  the  dietetic  origin  of  scurvy. 
The  result  was  inevitable — five  to  six  months  after  the 
ships  were  out  of  touch  with  land,  the  majority  of  the 
crew  frequently  were  incapacitated  by  this  disease, 
thereby  wrecking  many  an  expedition.2 

The  earliest  account  of  the  outbreak  of  scurvy  at  sea 
is  that  of  Vasco  cle  Gama,who  in  1497  discovered  a  passage 
to  the  East  Indies  by  way  of  the  Cape  of  Good  Hope. 
The  narratives  of  subsequent  explorers,  especially  those 
of  Cartier  and  of  Drake,  are  replete  with  descriptions  of 
the  ravages  of  scurvy.  The  expedition  of  Lord  Anson 
in  1740  is  always  cited  as  a  memorable  example  of  an 
undertaking  which  foundered  as  the  result  of  scurvy. 
After  a  cruise  of  four  years,  this  expedition  had  lost  from 
this  disease  more  than  four  out  of  five  of  the  original 
number  of  its  crews.  In  striking  contrast  to  this  picture, 
and  to  that  furnished  by  the  voyages  of  earlier  navigators, 
is  that  of  Captain  Cook,  who  in  1772  undertook  a  voyage 

3  The  fact  that  crews  of  vessels  which  set  sail  in  winter  were  more  sub- 
ject to  scurvy  than  those  which  set  out  in  the  summer  must  be  attributed  to 
the  existence  of  latent  scurvy  among  the  sailors  at  the  time  of  sailing,  rather 
than  to  the  season  of  the  year. 


HISTORY  OF  SCURVY  9 

lasting  over  three  years,  sailing  from  52°  north  to  71° 
south,  with  a  loss  of  but  one  of  his  crew  from  disease, 
and  that  not  from  scurvy.  This  remarkable  feat,  more 
than  any  other,  centered  attention  on  the  feasibility  of 
preventing  scurvy,  and  resulted  in  measures  tending  to 
eradicate  it  from  the  navy.  Captain  Cook  attributed  the 
absence  of  scurvy  among  his  crew  to  "sweetwort,"  an 
infusion  of  barley,  which  he  prepared  fresh  and  served 
liberally.  He  also  prized  the  antiscorbutic  value 
of  sauerkraut. 

We  find  accordingly  in  1795,  at  the  instance  of  Sir 
Gilbert  Blaine,  that  improvements  were  introduced  in  the 
victualling  of  the  fleet.  As  the  result  of  a  regular  ration 
of  lemon  juice,  the  incidence  of  scurvy  fell  precipitously. 
It  is  due  largely  to  this  provision  that  between  the  years 
1779  and  1813,  according  to  the  statistics  of  Sir  Jay  Bar- 
row, the  morbidity  and  the  mortality  in  the  British  Navy 
was  decreased  by  75  per  cent. 

It  has  been  shown  that  it  took  a  generation  after  the 
efficacy  of  antiscorbutics  had  been  demonstrated  in  various 
expeditions,  for  an  antiscorbutic  to  be  included  in  the 
ration  of  the  navy.  The  merchant  marine  of  England  was 
far  more  conservative,  and  for  many  years  after  scurvy 
had  been  eradicated  from  the  navy  we  still  read  of  its 
occurrence  on  the  vessels  making  voyages  to  India,  China 
and  Ceylon.  Gradually,  however,  its  incidence  became 
less  and  less.  Its  toll  of  death,  before  preventive  meas- 
ures were  employed,  may  be  appreciated  from  the  fact 
that  it  has  been  estimated  that  scurvy  destroyed  more 
sailors  than  all  other  causes  incidental  to  sea  life,  including 
the  great  slaughter  of  naval  warfare.  Sir  R.  Hawkins 
stated  in  the  latter  part  of  the  sixteenth  century  that  he 
could  give  an  account  of  10,000  mariners  who  had  been 


10  SCURVY:    PAST  AND  PRESENT 

destroyed  by  scurvy  during  the  twenty  years  that  he  had 
been  at  sea. 

As  is  well  known,  scurvy  has  played  an  important  role 
in  Arctic  and  Antarctic  explorations,  and  has  been  the 
cause  of  the  failure  of  many  of  these  expeditions.  It  is 
now  realized  that  the  development  of  scurvy  is  quite  pre- 
ventable, that  if  a  sufficient  quantity  of  meat  (especially 
raw  meat)  is  consumed,  explorers  can  be  entirely  inde- 
pendent of  a  supply  of  fresh  vegetables.  This  fact  was 
brought  out  by  the  Arctic  Survey  Committee  (British), 
who  "were  appointed  to  enquire  into  the  causes  of  the 
outbreak  of  scurvy  in  the  recent  Arctic  expedition' ' 
(1877),  and  who  reported  that  it  may  result  from  an  ab- 
sence of  fresh  meat.  That  this  conclusion  was  sound  has 
been  proved  by  the  experiences  of  Nansen  and  of  Johan- 
sen,  who  wintered  safely  in  Franz-Josefsland  on  a  diet  of 
meat  and  bacon.  More  recently  Stefansson  has  carried 
out  successful  Arctic  explorations,  depending  entirely  on 
fresh  meat  as  antiscorbutic  foodstuff  and  making  no  pro- 
vision whatsoever  for  vegetable  food. 

Infantile  Scurvy. — Glisson,  to  whom  we  owe  the  first 
description  of  rickets,  likewise  was  the  first  to  recognize 
scurvy  in  infants.  In  his  classic  treatise  on  rickets,  writ- 
ten in  1668,  he  writes  as  follows : 

"The  scurvy  is  sometimes  conjoyned  with  the  affect. 
It  is  either  hereditary,  or  perhaps  in  so  tender  a  constitu- 
tion contracted  by  infection,  or  lastly,  it  is  produced  from 
the  indiscreet  and  erroneous  Regiment  of  the  infant,  and 
chiefly  from  the  inclemency  of  the  air  and  climate  where 
the  child  is  educated.' ' 

"The  scurvy  complicated  with  this  affect  hath  these 
signs :  1.  They  that  labor  under  this  affect  do  impatiently 
indure  purgations;  but  they  who  are  only  affected  with 


HISTORY  OF  SCURVY  11 

the  Eachites  do  easily  tolerate  the  same.  2.  They  are 
much  offended  with  violent  exercises,  neither  can  they  at 
all  endure  them.  But  although  in  this  affect  alone,  there 
be  a  kind  of  slothfulness  and  aversation  from  exercise,  yet 
exercise  doth  not  so  manifestly,  at  least  not  altogether 
so  manifestly  hurt  them,  as  when  the  scurvy  is  conjoyned 
with  the  Eachites.  3.  Upon  any  concitated  and  vehement 
motion  they  draw  not  breath  without  much  difficulty,  they 
are  vexed  with  diverse  pains  running  through  their  joynts, 
and  these  they  give  warning  of  by  theyr  crying,  the  motion 
of  the  Pulse  is  frequent  and  unequal,  and  somethimes  they 
are  troubled  with  a  Palpitation  of  the  Heart,  or  threat- 
ened with  a  Lypothymie,  which  Affects  are  for  the  most 
part  soon  mitigated,  or  altogether  appeased  by  laying 
them  down  to  rest.  4.  Tumours  do  very  commonly  appear 
in  the  Gums.  5.  The  urin  upon  the  absence  of  the  accus- 
tomed feavers  is  much  more  intense  and  increased." 

Glisson's  description  of  scurvy  was  entirely  lost  sight 
of,  overshadowed  by  his  description  of  rickets,  so  that 
for  over  two  hundred  years  no  word  of  infantile  scurvy  is 
to  be  found  either  in  the  English  or  other  literature. 
There  is  no  doubt  that  from  time  to  time  cases  must  have 
occurred,  but  they  were  looked  upon  probably  as  rickets  or 
as  a  manifestation  of  one  of  the  hemorrhagic  diseases. 

In  1859  Moeller  described  some  cases  which  evidently 
were  scurvy,  but  which  he  termed  "  acute  rickets/ '  He 
realized  that  they  presented  a  novel  clinical  picture  but 
failed  to  recognize  that  they  represented  a  disorder  quite 
distinct  from  rickets.3      This  article  was  followed  within 

3  Infantile  scurvy  is  frequently  termed  "  Die  Moellersche  Krankheit." 
There  seems  to  be  no  occasion  for  giving  Moeller  credit  for  discovering  this 
disease,  as  he  believed  that  he  was  dealing  with  rickets  merely  in  an  acute 
form.  He  recognized  the  clinical  similarity  to  scurvy,  but  in  one  of  his  cases 
sharply  differentiates  it  from  adult  scurvy  by  the  fact  that  "  lemon  juice 
and  fresh  vegetables  "  were  of  no  avail  in  the  treatment. 


12  SCURVY:    PAST  AND  PRESENT 

the  next  few  years  by  reports  of  other  German  writers 
(Bohn,  Steiner,  Foerster)  who,  accepting  Moeller's  point 
of  view,  considered  these  cases  merely  as  an  acute  form 
of  rickets.  They  were  led  to  this  erroneous  conclusion 
chiefly  on  account  of  the  lack  of  marked  involvement  of 
the  gums,  which  they  considered  an  essential  sign,  in- 
fluenced by  their  conception  of  adult  scurvy.  This  view- 
point has  pervaded  the  German  literature  even  to  the 
present  day,  when  it  is  still  considered  necessary  to  bring 
further  evidence  that  infantile  scurvy  in  its  pathogenesis 
and  pathology  is  identical  with  adult  scurvy. 

In  1871  Ingerslev,  an  assistant  of  Hirschsprung  in 
Copenhagen,  wrote  a  paper  on  "A  Case  of  Scurvy  in  a 
Child,"  which  is  quite  convincing.  Two  years  later  Jal- 
land,  an  English  physician,  reported  a  similar  case  of 
' '  Scurvy  in  a  Ten-Months-Old  Infant. ' '  In  1878  Cheadle 
reported  three  cases  of  infantile  scurvy  with  typical  tume- 
faction of  the  gums,  and  obscure  tenderness  of  the  legs, 
and  followed  this  paper  by  two  others,  which  appeared 
in  1879  and  1882.  Cheadle  clearly  recognized  the  disease 
as  scurvy.  However,  as  the  title  of  his  first  paper — 
' '  Three  Cases  of  Scurvy  Supervening  on  Rickets  in  Young 
Children  " — indicates,  he  considered  it  a  condition  en- 
grafted upon  rickets.  About  this  time  (1881)  Gee  pre- 
sented a  brief  but  accurate  account  of  five  cases  of  scurvy 
which  he  termed  " osteal  or  periosteal  cachexia." 

In  1883,  Barlow  published  his  classical  paper  on  this 
subject,  the  first  to  furnish  anatomical  proof  that  this  dis- 
order of  infants  presented  the  pathological  changes  char- 
acteristic of  adult  scurvy.  Previous  to  this  publication 
there  had  been  but  one  autopsy  report,  that  by  Moeller, 
which  had  been  incorrectly  interpreted.  The  work  of 
Barlow  was  accepted  remarkably  quickly  in  England  and 


HISTORY  OF  SCURVY  13 

in  America,  but  less  promptly  on  the  Continent.  This 
was  probably  due  to  the  fact  that  infantile  scurvy  was 
occurring  far  more  frequently  in  these  two  countries,  and 
that  the  subject  was  open  therefore  to  more  prompt 
investigation.  This  increased  prevalence  of  infantile 
scurvy  in  the  two  great  English-speaking  nations  has 
continued  to  the  present  time,  and  no  doubt  is  due  to 
the  extensive  employment  of  artificial  feeding  and  of  pro- 
prietary foods.  In  1894  not  less  than  106  cases  were  re- 
ported to  the  Academy  of  Medicine  of  New  York  City 
by  various  physicians,  and  in  1898  the  comprehensive 
investigation  of  the  American  Pediatric  Society  appeared, 
which  was  based  on  379  cases. 

It  was  soon  evident  that  infantile  scurvy  occurred  to 
a  greater  or  less  degree  throughout  the  civilized  world.  In 
France,  Monfalcon  had  reported  a  case  in  1820  which  is 
sometimes  referred  to  as  the  earliest  case  of  infantile 
scurvy  mentioned  in  the  literature.  It  relates,  however, 
to  an  older  child  and  was  published  as  a  case  of  scorbutic 
rickets.  Netter  was  one  of  the  first  in  France  to  recognize 
the  true  nature  of  the  disorder,  and  published  several 
papers  in  1898  describing  typical  cases.  Infantile  scurvy 
was,  however,  almost  unknown  in  that  country  until  what 
is  termed  "lait  maternise"  and  "lait  fixe"  came  into 
vogue.  This  is  apparent  from  a  table  prepared  by 
Lecornu,  which  gives  a  list  of  all  cases  in  the  French 
literature  between  1894  and  1904,  and  of  the  diets  on 
which  they  came  about.  The  former  of  these  milk  prepa- 
rations is  subjected  to  various  manipulations  and  then 
heated  to  a  temperature  above  the  boiling  point ;  the  latter 
is  shaken  violently  in  a  machine  to  render  the  fat  globules 
smaller,  and  is  then  sterilized  by  one  of  the  usual  methods. 

Switzerland  has  undergone  an  experience  similar  to 


14  SCURVY:    PAST  AND  PRESENT 

that  of  France.  Previous  to  1903  only  five  cases  of  infan- 
tile scurvy  had  been  published  from  that  country.  In  this 
year  Stoos  published  an  additional  five.  In  1907  Bern- 
heim-Karrer  reported  nine  cases,  all  of  which  had  devel- 
oped on  homogenized  milk,  a  process  very  similar  to  that 
employed  by  the  French  to  break  up  the  fat  globules.  The 
increase  of  infantile  scurvy  in  Switzerland  may  be  judged 
by  the  fact  that  a  commission  was  formed  in  the  following 
year  to  investigate  its  occurrence. 

In  Germany  there  was  for  many  years  continued  dis- 
cussion as  to  the  true  nature  of  scurvy.  Some  believed 
it  to  be  a  form  of  rickets,  others  a  form  of  scurvy;  still 
others  a  combination  of  scurvy  and  rickets.  Some  thought 
it  merely  hereditary  syphilis,  and  not  many  years  ago 
Naegeli  looked  upon  it  as  an  entity  distinct  from  scurvy 
on  rickets.  The  subject  attained  additional  importance 
through  an  epidemic  of  infantile  scurvy,  which  broke  out 
in  Berlin  in  1898,  among  infants  who  received  milk  from 
one  of  the  largest  dairies.  The  episode  led  to  prolonged 
discussion  in  the  Berlin  Medical  Society,  and  to  several 
excellent  papers,  among  which  that  by  Neumann  deserves 
particular  mention. 

The  disorder  has  been  reported  inHollandbyDeBruin, 
who  recorded  numerous  cases;  in  Denmark,  by  Hirsch- 
sprung, who  refused  to  recognize  its  scorbutic  nature ;  in 
Italy,  by  Concetti,  and  by  others.  It  was  not  long  before 
there  were  reports  of  cases  from  almost  every  part  of 
the  world,  including  Australia  (Money)  and  East 
India  (Nichols). 

In  view  of  the  fact  that  scurvy  is  endemic  among 
adults  in  Russia,  we  should  also  expect  to  find  infantile 
scurvy  widespread  in  that  country.  In  point  of  fact,  quite 
the  contrary  seems  to  be  the  case.    In  connection  with  the 


HISTORY  OF  SCURVY  15 

great  scurvy  epidemic  in  Eussia  (1898-99),  Tschudakoff 
personally  examined  over  10,000  persons  and  found  11.11 
per  cent,  of  the  people  sick  with  this  disease.  He  states 
that  in  the  course  of  this  large  experience  he  did  not  meet 
with  a  single  case  under  the  age  of  five  years.  Fuerst 
writes  that  Filatow,  the  great  Russian  children's  special- 
ist, declared  that  he  knew  of  no  case  of  Barlow's  disease 
described  in  the  Russian  literature.  This  is  not  literally 
correct,  as  Doepp  described  an  epidemic  of  scurvy  in  the 
St.  Petersburg  Foundling  Asylum  occurring  in  1831.  It 
serves  to  emphasize,  however,  the  paucity  of  cases  among 
infants  in  this  great  land  of  endemic  adult  scurvy.  Lyab- 
mow,  in  referring  to  the  scurvy  in  Kazan,  tells  us  that 
among  28,000  cases  only  a  few  infants  were  affected,  and 
Rauchfuss  made  the  statement  at  the  International  Con- 
gress at  Copenhagen,  in  1884,  that  although  he  had  seen 
a  great  many  cases  of  scurvy,  he  had  never  seen  it  in 
children  one  to  two  years  of  age.  We  shall  not,  in  this 
place,  comment  on  this  interesting  and  apparently  para- 
doxical situation,  but  shall  have  occasion  to  refer  to  it  in 
considering  the  pathogenesis.  It  may  be  added  that  in 
Norway  and  Sweden,  where  scurvy  is  to  some  extent  also 
endemic  among  the  adult  population,  there  is  a  similar 
lack  of  scurvy  among  infants. 

Scurvy  in  the  World  War.— The  greatest  advance  in 
medicine  during  the  past  generation  has  been  in  the  fields 
of  hygiene  and  preventive  medicine.  One  might  therefore 
have  expected  that  the  World  War  would  have  differed 
from  previous  wars  in  a  notable  absence  of  scurvy  among 
the  troops  and  the  civilian  population.  This  is  true  to  a 
limited  degree  only.  Reports  which  have  been  published 
in  the  course  of  the  war,  and  especially  since  hostilities 
have  ceased,  show  that  the  troops  who  were  incapacitated 


16  SCURVY:    PAST  AND  PRESENT 

by  scurvy  must  have  numbered  many  thousands.  As  was 
to  be  expected,  scurvy  occurred  most  often  in  Russia, 
where  it  is  endemic.  The  largest  number  of  cases  was 
reported  by  Boerich,  who  as  director  of  a  Red  Cross 
Central  Station  in  Russia  saw  1343  cases.  Other  German 
physicians  who  had  charge  of  caring  for  the  Russian 
prisoners  give  accounts  of  the  occurrence  of  some  hun- 
dreds of  cases  of  scurvy.  An  article  by  Much  and  Baum- 
bach  gains  added  interest  from  the  novel  suggestion  that 
scurvy  is  transmitted  by  means  of  vermin.  That  scurvy 
must  have  reached  large  proportions  is  shown  by  the  fact 
that  in  July,  1916,  a  medical  commission  was  sent  by  the 
Germans  to  investigate  the  scurvy  in  a  Russian  army 
corps,  and  that  it  was  necessary  to  establish  for  this  dis- 
ease in  every  division  a  sanatorium  comprising  100  beds. 
Hoerschelman,  who  wrote  an  account  of  this  investigation, 
blames  the  bad  hygienic  surroundings,  the  lack  of  sleep, 
the  overexertion,  as  well  as  the  deficiency  of  food,  for  the 
occurrence  of  the  epidemic.  As  usual,  very  few  cases 
occurred  among  officers.  He  describes  a  number  of  in- 
stances where  scurvy  was  feigned  by  rubbing  the  gums 
and  making  them  bleed,  or  by  irritating  them  with  the 
juice  of  tobacco.  These  reports  on  scurvy  in  Russia  bring 
us  little  new  from  a  purely  medical  standpoint.  They 
emphasize  the  occurrence  of  night-blindness  as  an  early 
and  frequent  symptom.  It  is  difficult  to  judge  whether  this 
manifestation  was  due  entirely  to  the  scurvy,  or  was  in 
part  the  result  of  other  deficiencies  in  the  diet.  For  in- 
stance, Hift  states  that  the  night-blindness  was  cured  by 
cod  liver  oil,  or  by  the  water  in  which  beef  liver  had  been 
cooked.  This  would  point  rather  to  a  deficiency  of  the 
fat-soluble  vitamine,  as  these  substances  could  have  little 
effect  in  curing  scurvy.     The  cases  reported  by  Was- 


HISTORY  OF  SCURVY  17 

sermann,  where  neuritic  pains  in  the  legs  played  a  con- 
siderable role,  evidently  are  also  not  simple  scurvy,  but 
may  well  be  the  result  of  more  than  one  food  deficiency 
or  a  complicating  ostitis.  In  the  same  way  some  reports 
show  clearly  that  "hunger  edema"  complicated  scurvy. 

Scurvy  occurred  next  in  frequency  among  the  nations 
neighboring  Russia.  Speyer  tells  us  that  a  German  sani- 
tary commission  was  sent  to  Bulgaria  largely  with  the 
object  of  investigating  scurvy  in  that  country.  The 
excellent  monograph  on  the  pathology  of  scurvy  just 
written  by  Aschoff  and  Koch  was  founded  on  an  experi- 
ence in  Roumania  among  Turkish,  German  and  Austrian 
soldiers.  Added  to  its  other  woes  the  Servian  army  was 
visited  by  scurvy.  Wiltshire  gives  us  a  description  of 
this  disease  based  on  an  observation  of  3000  cases  in  the 
first  half  of  the  year  1917.  In  regard  to  scurvy  in  this 
part  of  the  world,  Morawitz  writes  that  when  he  reached 
Roumania  he  was  surprised  to  find  scurvy  the  most  preva- 
lent disease  in  the  army,  and  that  since  the  spring  of  1917 
it  was  widely  disseminated  among  the  German  troops. 
Lobmeyer  writes  of  scurvy  among  the  Turkish  troops, 
and  Disque  reports  500  cases  among  prisoners  captured 
in  Turkestan. 

Along  the  Western  front  very  few  cases  are  described. 
There  is  an  account  by  Korbsch  of  51  cases  in  this  area  in 
1915.  Schreiber  describes  30  cases  among  the  German 
prisoners  of  war  captured  in  the  beginning  of  1917,  which 
were  diagnosed  as  purpuric  rheumatism.  Arneth  recounts 
that  sporadic  cases  of  scurvy  occurred  amongthe  German 
troops,  especially  among  the  older  soldiers,  and  that  in 
many  cases  this  was  combined  with  the  hunger  edema. 
He  attributes  the  scurvy  to  a  dependence  on  dehydrated 
vegetables  in  the  ration. 

2 


18  SCURVY:    PAST  AND  PRESENT 

From  all  these  accounts  it  is  evident  that  scurvy  played 
an  important  role  in  the  general  nutrition  of  the  troops 
on  the  Eastern  front.  Probably  it  was  of  the  latent 
variety,  which  is  exceedingly  difficult  to  diagnose,  but 
which  increases  the  susceptibility  to  infection,  and  intensi- 
fies the  severity  of  all  medical  or  surgical  diseases.  Von 
Niedner  takes  this  point  of  view,  stating  that  although 
scurvy  had  been  largely  prevented  in  this  war,  the  obscure 
rudimentary  type  had  not  been  eradicated.  He  remarks 
upon  a  fact,  noted  in  our  Civil  War  and  other  wars,  that 
under  these  conditions  eruptions  assume  a  hemorrhagic 
character  in  typhoid  fever,  cerebrospinal  fever,  rheuma- 
tism and  other  infections.  Pick  made  a  similar  observa- 
tion at  a  medical  meeting  in  Vienna  in  reference  to  scurvy 
in  the  Austrian  army,  drawing  attention  to  the  hemor- 
rhagic diathesis  existing  among  the  troops  and  expressing 
the  opinion  that  scurvy  was  occurring  in  this  war  as  in 
previous  wars. 

Very  little  scurvy  seems  to  have  broken  out  among  the 
British  troops  in  Europe.  Thirty-two  cases  were  reported 
as  occurring  in  the  middle  of  1915  at  a  divisional  rest 
station  in  France.  It  made  marked  inroads,  however,  on 
the  health  of  the  Colonial  troops  in  Mesopotamia.  In  the 
report  of  the  Mesopotamia  Commission  we  read  that  7500 
men  were  lost  to  the  force  in  19  weeks  as  a  result  of 
scurvy,  and  that  this  happened  in  the  summer  of  1916 
although  additions  had  been  made  to  the  ration  in  the 
previous  spring.  A  conception  of  the  extent  of  the  scurvy 
may  be  formed  from  the  accompanying  table,  published 
by  Willcox : 

Scurvy  Beriberi 

(Indians)  (British) 

1 91 6  (July  1—  Dec.  31) 11,445  104 

1917   2,199  84 

1918 825  51 


HISTORY  OF  SCURVY  19 

It  will  be  noted  that  thousands  of  cases  occurred 
among  the  Indian  troops.  This  was  due  to  the  fact 
that  the  British  ate  more  potatoes  and  fresh  meat. 
In  his  official  report  of  the  outbreak  of  scurvy  among 
Indian  troops,  Colonel  Hehir  writes : ' '  The  only  vegetable 
now  allowed  is  2  ounces  of  potatoes  and  the  only  fresh 
meat  28  ounces  a  week.  It  is  very  doubtful  whether  this 
authorized  ration,  if  not  supplemented  by  other  vegetables 
and  more  meat,  is  sufficient  to  prevent  scurvy.' '  In  the 
account  which  this  officer  gives  of  the  medical  conditions 
during  the  siege  of  Kut-el-Amara,  it  is  stated  that  there 
were  1050  admissions  for  scurvy,  fully  developed,  incip- 
ient and  latent.  It  is  remarked  that  those  Indians  who  ate 
horseflesh  were  decidedly  less  affected.  From  the  fact 
that  special  hospitals  for  scurvy  were  established  in  June, 
1916,  at  Bagdad,  Amora  and  Basrah,  it  is  evident  that  a 
large  number  of  cases  must  have  been  encountered.  Most 
significant  in  this  connection,  however,  are  the  preventive 
measures  which  were  instituted  by  the  British  govern- 
ment. A  body  of  256  men,  designated  as  the  Madras 
Gardener's  Corps,  were  dispatched  to  Mesopotamia  to 
plant  gardens  all  over  the  country  and  to  supply  packets 
of  seeds  to  various  units.  At  Bagdad  alone  their  output 
of  vegetables  was  over  400,000  pounds.  This  certainly 
constitutes  a  remarkable  innovation  in  the  hygiene 
of  armies. 

The  French  army  was  not  entirely  spared  from  scurvy. 
In  1917  Harvier,  an  army  surgeon,  was  surprised  to  dis- 
cover that  95  per  cent,  of  the  800  troops  of  which  he  had 
charge  suffered  from  scurvy;  he  tells  us  that  other  epi- 
demic centres  were  recognized  later  outside  this  sector. 
Elsewhere  we  read  of  the  occurrence  of  scurvy  in  France, 
involving  40  per  cent,  of  the  1700  men  of  the  South  African 


20  SCURVY:    PAST  AND  PRESENT 

Labor  Corps,  and  that  this  disorder  was  still  more  serious 
in  another  company  owing  to  the  fact  that  it  was  not 
recognized  (Dyke).4  Benoit  reported  63  cases  which  he 
discovered  in  1917  among  300  laborers.  According  to  his 
account,  all  these  laborers  received  the  same  food,  and 
those  with  scurvy  recovered  quite  independently  of  any 
change  in  the  dietary. 

There  are  many  accounts  of  scurvy  among  the  Italian 
troops.  Vannutelli  gives  a  description  of  an  epidemic 
of  some  200  cases  of  infectious  purpura  with  manifesta- 
tions of  hemorrhagic  scurvy.  Another  writer  informs  us 
that  in  June,  1916,  scurvy  broke  out  among  some  Italian 
troops  stationed  at  an  altitude  of  1500  to  2000  metres 
(Gingui).  Vallardi  gives  an  account  of  180  cases  among 
Italian  troops  in  Macedonia,  accompanied  by  slight  jaun- 
dice and  enlargement  of  the  glands. 

The  American  soldiers  seem  to  have  been  practically 
spared  from  scurvy.  This  was  due  probably  to  their 
ample  ration  and  to  the  fact  that  they  were  in  the  field 
for  a  comparatively  short  period.  The  Surgeon-General 's 
report  to  date,  which  has  been  kindly  furnished  me,  showed 
but  5  cases  in  1917  occurring  in  Europe  and  the  United 
States,  and  but  15  cases  reported  during  the  year  1918. 

The  civilian  population  of  the  various  warring  coun- 
tries was  by  no  means  spared.  There  are  no  reports 
from  Russia  to  indicate  the  extent  of  scurvy,  but  from 
what  is  known  of  the  food  conditions  prevailing  there 

4  The  writer  adds  that  he  believes  that  the  health  of  the  natives  at 
home  is  protected  by  Kaffir  beer,  which  they  consume  even  to  the  amount 
of  3  gallons  a  day,  and  which  is  made  from  germinated  Kaffir  corn.  This 
cereal  is  germinated  by  steeping  it  in  water  for  forty-eight  hours  and  is 
then  dried  in  the  sun.  Only  enough  is  prepared  for  one  brew.  The  French 
prepared  a  similar  fermented  beverage  for  these  South  African  laborers; 
the  sole  difference  in  its  mode  of  preparation  was  that  the  corn  had  not 
been  ;rerminate<l. 


HISTORYfeOF  SCURVY  21 

toward  the  end  of  the  war,  one  can  be  certain  that  the 
number  must  have  been  large.  The  greatest  amount  of 
scurvy  has  been  reported  from  Austria,  more  particularly 
from  Vienna.  Previous  to  the  war  scurvy  was  a  rare 
disease  in  this  city,  both  among  adults  and  infants.  Dur- 
ing the  war,  however,  as  the  result  of  a  lack  of  fresh  food 
and  the  dependence  on  dehydrated  vegetables,  a  large 
number  of  cases  developed.  Tobler  reports  over  200  cases 
in  children  between  the  ages  of  two  and  fifteen  years, 
which  occurred  in  1917  in  child-caring  institutions  where 
the  milk  supply  was  markedly  deficient,  where  fresh  vege- 
tables were  lacking,  and  the  supply  of  potatoes  gave  out 
about  Christmas,  1916.  A  conception  of  the  deficiency 
of  the  milk  supply  may  be  gained  from  the  statement  that 
there  were  but  sixteen  quarts  a  day  for  about  1500  people. 
Some  of  these  children  were  undergoing  fresh-air  treat- 
ment and  were  out  of  doors  in  the  ' '  sun  stations ' '  day  and 
night.  For  the  cure  of  these  children  a  simple  decoction 
of  fir-tops  was  used,  a  therapeutic  procedure  stated  by 
Lind  to  have  been  of  value  in  the  Russo-Swedish  War 
of  1708. 

That  scurvy  must  have  occurred  extensively  among 
the  infants  in  Vienna  may  be  gathered  from  the  report  of 
Erdheim,  who  records  31  autopsies  on  infants  under  the 
interesting  title  of  the  i  l  Barlow  Heart. ' '  In  Berlin  scurvy 
occurred  also  in  the  foundling  asylums,  as  reported  by 
Eric  Mueller  and  by  Brandt.  This  was  caused  by  a  diet 
of  pasteurized  milk  and  dehydrated  vegetables.  In  an 
article  bearing  the  suggestive  title  of  "  On  a  Marked  In- 
crease in  Barlow's  Disease  in  the  lrears  of  the  War 
1917-1918,"  Epstein  states  that  in  Prague  there  had  been 
an  endemic  increase  of  infantile  scurvy  since  August,  1917. 
The  only  information  regarding  scurvy  among  the  adult 


22  SCURVY:    PAST  AND  PRESENT 

civilian  population  of  Germany  is  that  furnished  by 
Morawitz,  who  states  that  this  disorder  occurred  sporadi- 
cally. Here  again  it  is  probable  that  there  were  many 
latent  or  rudimentary  cases  which  were  not  recognized. 

In  Great  Britain  there  are  reports  which  show  that 
scurvy  manifested  itself  in  institutions  caring  for  the 
poor.  In  Glasgow  we  learn  of  50  cases  developing  in  the 
Poor  Law  Hospital  in  the  course  of  fifteen  months,  and 
in  Newcastle  of  16  cases  appearing  in  the  Poor  Law 
Infirmary  in  the  course  of  three  months. 

It  is  probable  that  when  more  detailed  reports  are 
available,  it  will  be  found  that  there  was  far  more  scurvy 
than  was  appreciated  during  the  course  of  the  war.  It 
will  be  impossible,  however,  to  gain  even  an  approximate 
knowledge  of  the  extent  to  which  this  disorder  prevailed, 
as  in  many  instances  it  was  inextricably  interwoven  with 
other  nutritional  diseases.  The  situation  which  Enright 
describes  in  Cairo  among  the  Turkish  prisoners  suffering 
from  war  edema,  where  there  was  '  •  evidently  a  scorbutic 
factor  involved,' '  probably  held  true  for  many  other 
parts  of  the  world.  War  and  scurvy  must  still  be  regarded 
as  associated  evils,  for  war  is  closely  linked  with  famine 
and  food  deprivation — the  dominant  factor  in  the  produc- 
tion of  scurvy. 


CHAPTER  II 
PATHOGENESIS  AND  ETIOLOGY 

At  the  outset  it  may  be  stated  that  there  is  no  longer 
any  reason  to  doubt  that  adult  scurvy  and  infantile  scurvy 
are  one  and  the  same  disease,  having  an  identical  patho- 
genesis. For  many  years,  far  longer  than  the  facts  war- 
ranted, there  was  discussion  whether  Barlow's  disease 
was  true  scurvy  or  merely  a  form  or  a  complication  of 
rickets,  or  perhaps  a  distinct  hemorrhagic  disease.  This 
question  may  be  relegated  to  the  past,  so  that  we  may 
proceed  to  consider  the  pathogenesis  of  scurvy  in  the 
infant  and  in  the  adult  under  a  common  heading. 

There  is  no  need  of  studying  all  the  theories  which 
have  been  advanced  to  account  for  scurvy.  They  have 
been  manifold  and  most  of  them  have  died  a  natural  death. 
For  many  years  the  potassmm  deficiency  theory,  sug- 
gested by  Garrod,  gained  wide  acceptance.  That  scurvy 
should  be  attributed  to  a  lack  of  this  salt  is  readily  com- 
prehensible in  view  of  the  abundance  of  potassium  in  the 
antiscorbutic  foodstuffs,  the  fruits  and  the  vegetables. 
It  was  not  long  before  it  was  evident  that  this  was  not 
the  correct  solution,  as  the  salts  of  potassium  served 
neither  to  prevent  nor  to  cure  scurvy.  This  theory  was 
accordingly  modified  to  include  only  organic  potassium. 
Experiment,  however,  failed  to  support  the  validity  of  this 
hypothesis,  and  it  was  gradually  abandoned. 

Another  theory  which  had  a  short  but  popular  career 
was  the  citric  acid  theory,  which  was  maintained  vigor- 
ously by  Netter.  This  explanation  seemed  logical  in  view 
of  the  marked  potency  of  the  citrous  fruits,  and  particu- 

23 


24  SCURVY:    PAST  AND  PRESENT 

larly  when  it  was  shown  that  human  milk  contains  a 
greater  percentage  of  the  salts  of  citric  acid  than  cow's 
milk,  and  that  some  of  these  salts  are  lost  in  the  course 
of  heating.  This  hypothesis  withstood  neither  the  practi- 
cal test  nor  chemical  investigation.  It  was  found  that  the 
various  salts  of  citric  acid,  either  singly  or  in  combination, 
are  unable  to  cure  scurvy.  This  treatment  has  been  em- 
ployed repeatedly  on  man  and  on  animals  with  little  or 
no  success;  we  also  have  resorted  to  it  in  vain.  It  was 
shown,  furthermore,  that  it  rested  on  an  insecure  chemical 
basis,  as  boiled  milk  contains  but  0.1  g.  per  litre  less  citric 
acid  than  raw  milk — an  amount  which  is  negligible  from 
a  therapeutic  point  of  view. 

Before  considering  what  may  be  termed  the  prevailing 
theories,  a  few  lines  must  be  devoted  to  the  acidosis  theory 
championed  by  Sir  Almroth  Wright.  According  to  this 
writer  scurvy  is  due  primarily  to  an  excess  of  acid  com- 
pared with  alkaline  food.1  A  theory  of  this  nature  was 
open  to  verification,  and  soon  collapsed  when  put  to  the 
test.  It  was  found,  in  the  first  place,  that  an  addition  of 
alkali  was  unable  to  cure  experimental  scurvy.  It  may 
be  added  that  we  have  found  it  of  no  value  in  infantile 
scurvy.  Hoist  and  Froelich  pointed  out  that  potatoes 
and  peas,  two  excellent  antiscorbutic  vegetables,  have  an 
alkaline  and  not  an  acid  ash;  that  adding  hydrochloric 
acid  to  dandelion  juice  improves  rather  than  diminishes  its 
potency;  that  1  g.  of  cabbage,  which  suffices  to  protect 
a  guinea-pig  from  scurvy,  does  not  contain  sufficient  alkali 
to  neutralize  an   acid   state;   and,  finally,   that   scurvy 

1  The  cases  on  which  Wright  based  his  theory  were  soldiers  who  de- 
veloped scurvy  during  the  siege  of  Ladysmith.  It  is  probable  that  the  men 
were  suffering  from  starvation,  purpura  and  dysentery.  That  they  did  not 
have  scurvy  is  proved  by  the  fact  that  they  were  cured  by  giving  lactate  and 
bicarbonate  of  soda. 


PATHOGENESIS  AND  ETIOLOGY  25 

is  not  encountered  in  the  well-established  acidosis 
of  diabetes. 

Let  us  turn  to  some  of  the  current  theories  of  the 
etiology  of  scurvy.  For  years  many  have  held  to  the  toxic 
theory,  believing  that  poisons  either  were  consumed  in  the 
food  or  formed  in  the  intestine  by  means  of  bacterial  ac- 
tion. At  present  this  view  is  held  by  the  minority.  The 
situation  in  this  respect  may  be  compared  to  that  of  beri- 
beri, about  which  there  is  also  no  consensus  of  opinion, 
a  minority  attributing  it  to  the  action  of  an  unknown  toxin. 

A  consideration  of  the  clinical  course  of  scurvy  sheds 
but  little  light  on  this  aspect,  and  can  be  interpreted  as  well 
for  as  against  the  action  of  a  toxin.  The  nervous  system, 
which  is  well  known  to  be  particularly  vulnerable  to  toxins, 
is  but  slightly  affected — the  cardiorespiratory  phenomena 
(indicating  an  involvement  of  the  pneumogastric  nerves), 
the  occasional  changes  in  the  optic  disks,  and  the  abnor- 
mality of  the  tendon  reflexes  constitute  the  aggregate.  In 
a  general  way  it  may  be  stated  that  the  symptoms  resem- 
ble those  brought  about  by  poisons  of  various  kinds — the 
cottonseed  poisoning  in  swine,  the  toxic  products  of  the 
wheat  embryo,  or  even  mercurial  poisoning  in  man.2  The 
nervous  symptoms,  especially  the  irritability  of  the  heart, 
remind  one  of  the  enterogenous  intoxication  or  entero- 
toxic  polyneuritis  described  by  Von  Noorden.  Such  analo- 
gies are  interesting  and  suggestive,  but  can  be  accorded 
little  weight  in  deciding  the  question  at  issue. 

If  a  toxin  is  to  be  regarded  as  the  proximate  cause  of 

2  In  chronic  mercurial  poisoning  the  following  suggestive  symptoms 
occur:  anemia,  bleeding  and  spongy  gums,  loosening  of  the  teeth,  a  quick- 
ened pulse,  ulcers  of  the  extremities.  At  times  mercury  attacks  the  nervous 
system,  producing  palsy.  The  resemblance  is  heightened  by  the  fact  that 
calcium  metastases  have  been  found  in  the  muscle  in  experimental  scurvy 
(Hart  and  Lessing)  comparable  to  those  characteristic  of  mer- 
curial poisoning. 


26  SCURVY:    PAST  AND  PRESENT 

infantile  scurvy,  the  question  naturally  arises  as  to  the 
nature  of  the  toxin.  Is  it  exogenous  or  endogenous? 
There  is  sound  basis  for  believing  that  the  hypothetical 
poison  is  not  introduced  preformed  in  the  food.  In  the 
first  place,  infantile  scurvy  frequently  develops  in  babies 
who  receive  milk  of  the  very  best  grade ;  indeed,  in  contra- 
distinction to  rickets,  this  is  not  preeminently  a  disease 
of  the  poor.  Furthermore,  there  is  no  relation  between 
the  concentration  of  the  food  mixture  and  its  liability  to 
induce  scurvy.  For  example,  if  among  a  large  number 
of  infants  receiving  pasteurized  milk  from  a  common 
source,  some  are  given  the  milk  diluted  by  one-half,  others 
given  it  diluted  by  one-third,  and  still  others  whole  milk, 
the  last  group  will  show  the  least  tendency  to  scurvy, 
which  we  should  not  expect  were  the  poison  contained 
in  the  food.  Nor  is  it  at  all  uncommon  to  encounter  scurvy 
in  an  infant  which  has  been  fed  with  a  very  dilute  milk 
mixture.  Another  side  of  this  question  should,  however, 
be  mentioned — stale  pasteurized  milk  is  more  apt  to  pro- 
duce scurvy  than  the  freshly  pasteurized,  but  here  again 
the  injury  is  in  inverse  ratio  rather  than  in  direct  ratio  to 
the  amount  consumed.  There  are  reports  of  adult  scurvy 
having  been  occasioned  by  decomposed  food,  such  as 
Torup's  investigation  of  Nansen's  polar  expedition,  but 
the  diet  had  not  been  faultless  in  other  respects.  The 
experiments  of  Jackson  and  Harley,  who  produced  scurvy 
in  monkeys  by  feeding  tainted  tinned  meat,  cannot  be  un- 
reservedly accepted,  as  they  are  substantiated  by  no 
pathological  examination  of  the  bones,  and  the  diarrhoea 
and  the  blood  and  mucus  in  the  stools  do  not  suggest  sim- 
ple scurvy. 

Of  those  who  held  to  the  toxic  origin  of  scurvy  the 
majority  had  in  mind  an  endogenous  toxin,  although  the 


PATHOGENESIS  AND  ETIOLOGY  27 

conception  of  the  nature  of  this  poison  varied  greatly. 
The  minority  report  of  the  American  Pediatric  Society 
states  that ' '  scurvy  appears  to  be  a  chronic  ptomaine  poi- 
soning due  to  the  absorption  of  toxins.' '  Neumann  con- 
sidered scurvy  a  chronic  poisoning,  formed  probably  from 
the  albumin  of  the  milk,  and  considered  the  fact  that  the  in- 
fant refused  to  take  the  harmful  food  as  weighty  evidence 
of  its  toxic  nature.  Kohlbrugge  included  scurvy  in  his 
group  of  "fermentive  diseases, "  due  to  the  overgrowth 
of  harmful  bacteria  in  the  intestine,  which  are  normally 
restrained  by  the  acid  reaction  of  the  chyme.  McCollum 
and  Pitz,  on  the  basis  of  a  study  of  experimental  scurvy, 
suggested  that  as  the  result  of  a  break  in  the  metabolism 
it  might  be  due  to  the  retention  of  fasces  and  consequent 
absorption  of  toxins.  Still  more  recently  Gerstenberger 
suggested  that  as  the  result  of  the  break  in  the  metabolism 
of  carbohydrates,  a  defunctioning  substance,  possibly 
oxalic  acid,  is  produced,  which  has  a  strong  affinity 
for  calcium. 

It  is  of  no  avail  to  discuss  these  various  hypotheses — 
the  formation  of  intestinal  toxins — except  where  they  are 
based  on  observations  which  can  be  tested  and  controlled. 
This  is  true  solely  of  the  relation  of  constipation  to  scurvy, 
and  we  shall  confine  ourselves  therefore  to  a  consideration 
of  this  aspect  of  the  question. 

There  can  be  no  question  whether  retention  of  faeces  of 
itself  can  bring  about  scurvy;  this  is  excluded  by  the 
marked  instances  of  constipation  frequently  encountered 
among  thriving  babies.  The  majority  of  bottle-fed  babies 
and  a  large  number  of  the  breast-fed  suffer  from  a  greater 
or  less  degree  of  constipation.  On  looking  over  our  rec- 
ords of  infantile  scurvy  from  this  point  of  view,  and  com- 
paring them  with  non-scorbutic  infants,  we  have  not 


28  SCURVY:    PAST  AND  PRESENT 

been  able  to  note  a  characteristic  distinction.  Some  of  the 
infants  had  normal  stools,  others  suffered  from  constipa- 
tion, while  the  records  of  a  great  number  showed  occa- 
sional loose  stools.  Furthermore,  in  cases  of  latent  or 
subacute  infantile  scurvy,  it  was  of  no  moment  whether  a 
laxative  was  given  or  whether  constipation  was  induced 
by  means  of  opium.  The  report  of  the  American  Pediatric 
Society  shows  that  the  majority  have  had  a  similar  ex- 
perience; the  bowels  were  regular  in  seventy-four  in- 
stances, irregular  in  fifteen,  constipated  in  one  hundred 
and  twenty-six,  and  diarrhoeal  in  seventy-seven.  In  this 
connection,  it  may  be  pointed  out  that  the  preparation 
termed  "malt  soup,"  the  diet  which  in  our  experience  has 
been  most  frequently  associated  with  scurvy,  is  essentially 
laxative,  and,  on  the  other  hand,  that  one  of  the  most 
potent  antiscorbutics  is  potato,  which  has  no  definite  laxa- 
tive property.  It  may  be  added,  as  noted  elsewhere,  that 
scurvy  developed  in  infants  in  spite  of  their  receiving  cod 
liver  oil  or  olive  oil  for  long  periods.  It  is  evident,  there- 
fore, that  the  retention  of  faeces  is  not  the  essential  factor 
in  the  etiology  of  scurvy.  Its  secondary  role,  especially 
after  scurvy  has  developed,  will  be  considered  later  in 
this  chapter. 

In  order  to  elucidate  this  question  Torrey  and  Hess 
made  a  study  of  the  relation  of  the  intestinal  flora  to  the 
scurvy  of  guinea-pigs  and  of  infants.  In  guinea-pigs  they 
found  in  the  intestinal  tract  merely  such  bacteria  as  are 
encountered  on  the  oats  and  hay  fed  these  animals.  The 
bacteria  were  few  in  number  and  hardly  any  were  actively 
proteolytic.  Furthermore,  there  was  no  change  in  the 
flora  on  adding  antiscorbutic  food,  although  the  scorbutic 
symptoms  disappeared.  Recently  Givens  and  Hoffman, 
as  the  result  of  a  similar  study,  have  come  to  the  same 


PATHOGENESIS  AND  ETIOLOGY 


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30  SCURVY:    PAST  AND  PRESENT 

conclusion.  The  investigation  of  infants  led  to  similar 
results,  and  is  illustrated  in  Table  1.  It  will  be  seen 
that  the  infants  were  all  on  a  high  carbohydrate  diet,  and 
that  in  two  instances  the  flora  was  compared,  not  only 
during  the  active  scorbutic  process,  but  after  orange  juice 
had  been  given  for  a  week  or  more.  The  bacteria  were 
such  as  one  should  expect  on  a  diet  rich  in  carbohydrates ; 
putrefactive  organisms  were  present  only  in  small  num- 
bers ;  and  in  the  case  in  which  they  were  most  numerous 
(S),  they  had  disappeared  upon  the  subsequent  examina- 
tion, although  the  scurvy  had  become  more  marked.  It  is 
evident,  therefore,  that  in  the  scurvy  of  infants  as  well 
as  of  guinea-pigs  there  is  no  overgrowth  of  putrefactive 
bacteria  in  the  intestinal  tract,  and  therefore  no  basis 
for  the  hypothesis  of  ptomaine  or  similar  intoxication. 
Other  poisons  may,  however,  be  absorbed  from  the  intes- 
tine as  the  result  of  a  prolonged  deprivation  of  an  essen- 
tial vitamine. 

There  are  those  who  believe  that  scurvy  is  of  bacterial 
origin,  some  going  so  far  as  to  regard  it  as  a  communi- 
cable disease.  This  viewpoint  was  maintained  by  the 
famous  Boerhaave  and  supported  with  all  the  weight  of 
his  authority  by  Villemin  in  the  seventeenth  century.  It 
is  a  view  held  by  many,  if  not  by  the  majority,  of  phy- 
sicians in  Russia  to-day,  and  recently  has  been  advanced 
by  European  army  surgeons.  This  question  illustrates 
in  an  interesting  manner  how  the  trend  of  the  day  in- 
fluences medical  thought — it  has  been  suggested  lately  by 
Much  and  Baumbach  that  the  scurvy  microorganism  may 
be  carried  by  means  of  lice.  But  clinical  experience  points 
absolutely  against  the  infectious  nature  of  scurvy.  In- 
deed, the  only  episode  which  lends  any  support  to  this 
opinion  is  its  widespread  and  seemingly  epidemic  charac- 


PATHOGENESIS  AND  ETIOLOGY  31 

ter ;  the  fallacy  of  such  deductions  has  been  well  illustrated 
in  regard  to  beriberi,  which  for  many  years  was  regarded 
as  an  infectious  and  communicable  disease.  The  fact  that 
whenever  scurvy  occurs  among  a  body  of  troops  the  offi- 
cers are  spared,  constitutes  convincing  evidence  against 
its  communicability.  This  peculiarity  of  incidence  was 
noted  by  Hoerschelman  and  others  in  the  recent  World 
War,  and  is  referred  to  in  the  Report  of  the  War  of  the 
Rebellion.  Many  of  the  earlier  writers,  in  discussing 
the  occurrence  of  ship  scurvy,  drew  attention  to  the  pau- 
city of  cases  among  the  officers. 

When  we  turn  to  bacteriological  studies  we  find  that 
some  years  ago  Ausset  claimed  to  have  isolated  "a  pas- 
teurella  type  of  organism ' '  from  a  case  of  infantile  scurvy, 
and  suggested  it  as  the  causative  agent  of  this  disorder. 
On  the  other  hand,  Hart,  Rehn,  Hirschsprung,  von  Starck, 
Schmorl,  and  recently  Boerich,  have  failed  to  find  bacteria 
in  the  blood,  although  the  total  number  of  cultures  must  be 
admitted  to  have  been  small.  Czerny  and  Keller  report 
negative  bacterial  growth  from  fluid  aspirated  from 
affected  joints. 

The  only  articles  considering  this  important  question 
from  the  experimental  side  are  those  of  Jackson  and 
Moody,  and  of  Moore,  who  conclude  tentatively  that 
scurvy  may  be  a  bacterial  infection.  Jackson  and  Moody 
cultivated  a  diplococcus  from  the  tissues  of  scorbutic 
animals  after  death,  reproduced  hemorrhages  by  inocu- 
lating cultures  of  these  microorganisms  into  the  circula- 
tion, and  recovered  the  bacteria  from  the  tissues  some 
weeks  later.  Their  results  are  open  to  the  criticism  that 
bacteria  were  found  only  after  death,  and  that  all  blood 
cultures  during  life  proved  negative.  An  article  by 
Moore,  however,  which  has  just  appeared  from  this  same 


32  SCURVY:    PAST  AND  PRESENT 

laboratory,  states  that  "an  organism  of  the  strepto- 
coccus viridans  type  was  isolated  from  the  blood"  in  a 
case  of  adult  scurvy.  In  one  instance  we  recovered  an 
organism  of  this  type  from  the  blood  of  an  infant  suffer- 
ing from  scurvy.  It  is  highly  important  that  more  blood 
cultures  should  be  carried  out  in  the  course  of  human 
or  animal  scurvy,  and  that  particular  note  should  be 
made  of  the  stage  of  the  disorder  when  they  are  taken. 

There  is  no  doubt  that  invasion  of  the  blood-stream 
does  occur  readily  in  the  course  of  scurvy,  but  this  takes 
place  generally  after  the  disease  has  developed  and  must 
be  regarded  as  a  secondary  phenomenon  and  therefore 
unessential  from  an  etiologic  standpoint.  Indeed  one  of 
the  striking  and  important  symptoms  of  scurvy  is  the 
marked  susceptibility  to  infection  (furunculosis,  nasal 
diphtheria,  " grippe,' ;  etc.),  which  comes  about  as  the 
result  of  the  nutritional  disturbance.  An  excellent  exam- 
ple of  this  interrelationship  is  the  " epidemic' '  of  hemor- 
rhagic scurvy  described  in  the  chapter  on  symptomatol- 
ogy. Hemorrhages  coming  about  in  this  way  should  be 
regarded  as  focal  complications  rather  than  as  truly  scor- 
butic. It  should  be  realized  that,  at  the  present  time, 
it  is  not  possible  to  distinguish  between  local  symptoms 
which  are  truly  nutritional  or  scorbutic  in  nature,  and 
those  which  are  bacterial  and  of  secondary  origin. 

The  newest  theory,  and  the  one  at  present  most  widely 
accepted,  is  the  vitamine  {accessory  factor)  theory.  It 
was  evident  to  Lind  in  the  seventeenth  century  that  scurvy 
could  be  prevented  and  cured  by  means  of  fruits  or  vege- 
tables, a  fact  which  became  increasingly  clear  to  succeeding 
generations.  Until  the  latter  part  of  the  nineteenth  cen- 
tury, however,  this  miraculous  virtue  of  plants  stimulated 
little  inquiry  and  no  research.    As  far  back  as  1841  Budd 


PATHOGENESIS  AND  ETIOLOGY  33 

realized  that  "the  explanation  depended  on  the  study 
of  organic  chemistry,  and  the  experiments  of  physiolo- 
gists, "  but  until  recently  it  was  not  perceived  that  the 
solution  of  the  problem  involved  the  introduction  of  a  new 
chemical  factor.  This  view  suddenly  took  shape  after 
Eijkman  in  1897  showed  the  nature  of  polyneuritis  in  fowl, 
and  Hopkins  in  1906,  going  a  step  farther,  demonstrated 
the  necessity  of  one  or  more  unidentified  food  factors  for 
the  normal  nutrition  of  the  rat.  The  work,  which  estab- 
lished this  novel  theory  on  a  scientific  basis  in  relation  to 
scurvy  was  the  classic  investigation  of  Hoist  and  Froelich, 
referred  to  so  frequently  in  connection  with  experimental 
scurvy.  These  investigators  showed  that  the  mere  diying 
of  vegetables  was  sufficient  to  deprive  them  of  their  anti- 
scorbutic power,  although  from  a  chemical  standpoint  they 
seemed  unaltered ;  that  high  degrees  of  heat  had  generally 
the  same  effect ;  that  under  certain  conditions  these  foods 
withstood  prolonged  heating,  demonstrating  that  the  anti- 
scorbutic factor  was  not  a  ferment ;  that  acids  and  alkalies 
played  no  essential  role  in  the  etiology;  that  fats,  proteins 
and  carbohydrates  were  not  significant  factors;  that  as 
little  as  1.0  g.  of  cabbage  suffices  to  afford  protection  to  a 
guinea-pig.  In  other  words,  by  a  process  of  exclusion 
they  showed  that  it  is  a  disorder  due  to  the  lack  of  an 
unidentified  food  factor. 

Subsequent  studies,  carried  out  within  the  past  few 
years,  have  served  only  to  strengthen  this  viewpoint.  For 
example,  an  "artificial  orange  juice"  composed  of  the 
various  salts,  citric  acid,  and  sucrose  in  the  proportions 
in  which  they  are  found  in  the  natural  juice,  failed,  in  the 
experience  of  Hess  and  Unger,  to  protect  or  to  cure 
guinea-pigs — demonstrating  that  this  preparation  did  not 
contain  the  essential  factor.  In  the  same  way,  Harden  and 

3 


34  SCURVY:    PAST  AND  PRESEN . 

Zilva  were  able  to  protect  animals  from  scurvy  with  a 
preparation  of  lemon  juice  which  had  been  almost  entirely 
deprived  of  its  salts.  It  is  needless  to  multiply  these 
examples.  It  is  sufficient  to  state  that  there  has  been 
no  investigation  during  the  last  years  of  intensive  study 
of  scurvy,  which  has  tended  to  weaken  the  vitamine 
hypothesis.  It  may  be  stated,  therefore,  that  experiments 
have  demonstrated  that  scurvy  is  due  essentially  to  the 
lack  of  a  specific  vitamine.  It  is  unwise  to  proceed  far- 
ther and  place  it  in  the  group  of  so-called  "  deficiency 
diseases,''  including  beriberi,  pellagra,  etc.,  unless  the 
reservation  is  made  that  these  several  diseases  may  pre- 
sent marked  differences.  It  is  quite  possible  that  one 
may  be  what  might  be  termed  a  simple  deficiency  disease, 
whereas  another  may  have  important  additional  etiologic 
factors.  At  any  rate,  unless  it  is  realized  that  there  has 
been  no  proof  that  all  are  due  to  similar  deficiencies,  we 
may,  by  stamping  them  all  alike  and  by  grouping  them 
together,  be  misled  into  taking  their  close  relationship  for 
granted..  In  regard  to  scurvy,  there  may  well  be  other 
etiologic  factors,  but  they  are  of  a  secondary  character. 
Bacterial  invasion  has  been  referred  to  in  this  connection, 
and  it  is  possible  that  toxins  are  absorbed  from  the  intes- 
tine after  nutrition  has  been  disturbed.  Diarrhoea  and 
digestive  disturbances  may  play  a  role.  Whether  the 
total  intake  of  food  or  the  correlation  of  its  constituents — 
protein,  carbohydrate,  fat  and  salts — affects  the  action 
of  the  vitamine,  is  one  which  has  not  been  well  studied 
clinically  or  experimentally.  In  regard  to  beriberi,  it  is 
claimed  that  there  is  a  direct  ratio  between  the  quantity  of 
carbohydrate  ingested  and  the  amount  of  vitamine  re- 
quired. No  such  interrelationship  exists  in  regard  to 
scurvy.    This  was  evident  a  few  years  ago  (1917)  when 


PATHOGENESIS  AND  ETIOLOGY  35 

some  infants  receiving  pasteurized  milk,  prepared  with 
the  addition  of  3  per  cent,  flour,  did  not  tend  to  develop 
scurvy  more  readily  than  others  receiving  simple  pasteur- 
ized milk.  A  consideration  of  the  antiscorbutic  vitamine 
will  be  postponed  for  a  subsequent  chapter. 

Etiology. — In  considering  infantile  scurvy  we  are  con- 
cerned almost  entirely  with  the  artificially-f  ed  baby.  It  is 
true  that  in  the  literature  we  meet  with  scattered  reports 
of  scurvy  in  breast-fed  babies  and  that  these  cases  seem 
to  constitute  a  noteworthy  group;  in  point  of  fact,  they 
are  comparatively  few.  The  collective  investigation  of 
the  American  Pediatric  Society  includes  ten  infants  who 
had  been  given  breast  milk  exclusively,  and  Concetti  adds 
another  ten  in  his  compilation  of  682  cases.3  In  spite 
of  their  paucity  these  cases  require  separate  considera- 
tion because  they  represent  an  important  aspect  from 
an  etiologic  standpoint.  How  are  we  to  explain  the 
fact  that  human  milk  may  lead  to  rather  than  pro- 
tect against  this  disorder?  On  investigating  more 
closely  it  is  found  that  these  cases  differ  in  several 
important  respects  from  the  group  which  has  been  arti- 
ficially fed.  They  are  of  a  different  age ;  instead  of  being 
in  the  second  half  year  of  life  they  are  generally  but  a 
few  months  old.  Furthermore,  the  signs  are  not  the  same. 
The  hemorrhages  involve  the  upper  extremities  fully  as 
frequently  as  the  lower  extremities,  and  often  appear  at 
unusual  sites — for  example,  on  the  scalp  or  as  large  sub- 
cutaneous effusions  at  various  parts  of  the  body.  In 
many  instances  it  has  been  noted  that  the  nursing  mothers 
were  suffering  from  some  debilitating  disease  such  as 

3  These  figures  constitute  an  irrefutable  argument  against  the  statement 
frequently  made  that  a  monotonous  diet  leads  to  scurvy.  It  is  only  when  the 
monotonous  diet  does  not  contain  an  adequate  quantity  of  antiscorbutic 
vitamine  that  it  is  to  be  feared. 


36  SCURVY:    PAST  AND  PRESENT 

tuberculosis  or  syphilis,  or  had  an  insufficient  supply  of 
milk,  or  that  there  had  been  some  other  unusual  factor, 
as  Freund  has  shown  in  an  article  devoted  to  this  par- 
ticular aspect.  It  is  not  necessary,  however,  to  fall  back 
on  these  attendant  circumstances  to  exclude  from  con- 
sideration many  of  the  cases.  For  example,  Crandall's 
case  of  "scurvy  in  an  infant  of  six  weeks"  should  be  in- 
validated, not  because,  as  Freund  suggests, the  mother  had 
rheumatism  and  insufficient  milk,  but  because  of  the  age 
of  the  infant,  and  the  course  of  the  disease ;  first  one  arm 
was  involved,  then  the  other,  then  hemorrhages  appeared 
on  the  skin,  and  finally  it  was  cured  by  giving  a  teaspoon- 
ful  of  fresh  cream  before  each  nursing.  Had  the  baby 
really  suffered  from  scurvy  it  could  not  have  been  cured  by 
this  means.  Southgate's  case  must  also  be  rejected,  not 
because  the  mother  was  tuberculous  but  in  view  of  the 
symptoms — the  arms  and  legs  were  pseudoparetic,  "the 
legs,  feet  and  hands  were  double  their  normal  size,"  and 
moderately  large  hemorrhages  were  present  on  the  back 
and  chest.  It  seems  hardly  necessary  to  discuss  in  detail 
the  score  of  cases  which  comprise  this  group,  as,  in  gen- 
eral, the  same  criticism  applies  to  all.  Some  evidently 
were  congenital  syphilis,  still  more  must  be  regarded  as 
sepsis,  and  others  as  unknown  toxic  conditions.  Apart 
from  these  cases  the  question  must  be  considered  whether 
scurvy  can  occur  in  a  breast-fed  infant.  Personally,  we 
have  never  met  with  a  case  of  this  kind,  and,  as  Finkel- 
stein  aptly  remarks,  there  has  been  "no  necropsy  of  a 
breast-fed  case  or  conclusive  X-ray  picture."  It  seems 
possible  only  if  an  infant,  for  a  period  of  months,  has 
obtained  a  scanty  supply  of  milk,  or  when  the  milk  has 
been  exceedingly  deficient  in  the  antiscorbutic  vitamine. 


PATHOGENESIS  AND  ETIOLOGY  37 

Even  under  such  conditions  it  does  not  seem  possible  for 
scurvy  to  become  manifest  in  six  weeks  (Crandall's  case), 
or  in  four  weeks,  as  in  a  case  reported  by  the  American 
Pediatric  Society,  unless  we  believe  that  the  infant  suf- 
fered also  from  a  certain  degree  of  intrapartum  or  con- 
genital scurvy.  In  view  of  the  fact  that  an  infant 
requires  about  one  pint  of  milk  to  furnish  it  with  an  ade- 
quate daily  quota  of  the  antiscorbutic  factor,  it  is  theo- 
retically possible,  under  extreme  conditions,  for  it  to 
become  scorbutic,  in  spite  of  being  nursed  at  the  breast. 
Such  an  occurrence  must  be  regarded  as  exceedingly  rare, 
far  more  so  than  the  current  statistics  illustrate,  for  con- 
siderably less  than  a  pint  of  milk  a  day  will  prevent  the 
appearance  of  manifest  scurvy  for  a  period  of  several 
months.  Some  of  the  reported  cases  may  have  been 
latent  scurvy,  rendered  acute  by  a  complicating  bac- 
terial infection. 

It  might  be  expected  that  by  ascertaining  the  occur- 
rence of  infantile  scurvy  in  countries  ivhere  it  is  endemic, 
we  could  learn  under  what  conditions  and  how  frequently 
breast-fed  babies  develop  this  disorder.  Approaching  the 
question  from  this  angle,  it  is  found  that  the  available  data 
is  meagre  and  not  entirely  convincing.  Peculiarly  enough 
infantile  scurvy  has  rarely  been  reported  from  Russia, 
where  scurvy  is,  in  many  sections,  endemic.  For  example, 
although  Tschudakoff,  who  personally  examined  over 
10,000  persons,  in  connection  with  the  great  scurvy  epi- 
demic in  Russia  (1898-99)  found  11.11  per  cent,  of  the  peo- 
ple suffering  from  this  disease,  he  did  not  meet  with  a 
single  case  under  the  age  of  nve  years.  Fuerst  writes  that 
Filatow,  the  celebrated  Russian  children's  specialist,  de- 
clared that  he  knew  of  no  instance  of  Barlow's  disease 


38  SCURVY:,,  PAST  AND  PRESENT 

described  in  the  Russian  literature.4  Shortly  after  the 
recent  war  scurvy  broke  out  among  the  wet-nurses  in  an 
infant  asylum  in  Vienna.  A  very  few  of  the  infants  nursed 
by  these  women  developed  the  disorder,  far  fewer  than 
might  have  been  expected  (personal  communication). 
Hopkins  recently  wrote  a  communication  to  the  effect  that 
in  the  island  of  Aruba,  in  the  Dutch  West  Indies,  they  had 
been  unable  to  grow  any  crops  in  1912,  1913,  1914,  that 
3000  cases  of  scurvy  had  developed  there  during  the  year 
1915,  and  that  in  1917  it  was  again  being  noted.  In  answer 
to  a  personal  inquiry  regarding  the  occurrence  of  scurvy 
among  the  infants  of  Aruba,  he  wrote  that  "infantile 
scurvy  is  very  rare,"  although  "most  all  of  the  babies  are 
breast-fed  for  about  a  year. '  * 

On  the  other  hand,  descriptions  of  the  coincidence 
of  scurvy  in  mother  and  nursling  are  even  more  fragmen- 
tary; in  fact,  we  have  been  able  to  find  but  two  reports 
of  this  kind.  The  one  most  frequently  cited  is  that  of 
Cheadle,  which  consists  merely  of  the  following  bald  state- 
ment: "With  the  exception  of  one  or  two  doubtful  cases, 
of  which  the  details  of  breast-feeding  and  diet  are  imper- 
fectly given,  the  only  instances  of  scurvy  arising  in  suck- 
lings are  those  when  the  nursing  mother  has  been 
suffering  from  scurvy  at  the  time."  The  other  report 
has  been  gleaned  from  a  recent  editorial  in  the  British 
Medical  Journal,  which  refers  to  the  above  mentioned  out- 
break of  scurvy  in  Vienna,  affecting  in  some  cases  both 
mothers  and  breast-fed  infants. 

It  is  difficult  to  pass  judgment  on  this  question  in  view 

4  This  is  not  literally  correct,  as  Doepp  described  an  epidemic  of  scurvy 
in  the  St.  Petersburg  Foundling  Asylum  occurring  in  1831. 

&  During  1919  in  Aruba  there  were  293  births  and  30  deaths  under  one 
year,  mo.st  of  these  deaths  being  due  to  intestinal  diseases.  The  mothers 
subsist  mainly  on  maize  or  guinea  small  corn,  with  some  goat  and  sheep 
meat,  and  a  little  fresh  fish,  but  no  vegetables  or  fruit.  The  water  is  brackish. 


PATHOGENESIS  AND  ETIOLOGY  39 

of  the  paucity  of  data.  In  the  near  future,  probably,  when 
we  learn  in  detail  about  the  epidemics  of  scurvy  which 
occurred  during  and  immediately  following  the  war,  we 
shall  be  in  a  better  position  to  weigh  its  pros  and  cons. 
In  view  of  the  above  data  it  does  not  seem  that  nursing- 
infants  readily  develop  scurvy,  even  though  their  mothers 
do  not  obtain  a  full  quota  of  antiscorbutic  vitamine  in  their 
food.  This  appears  to  be  the  clinical  result,  whatever  its 
interpretation  may  be.  It  cannot  be  explained  on  the 
assumption  that  human  milk  contains  a  particularly  large 
quota  of  this  factor.  In  a  test  carried  out  to  elucidate  this 
question  it  was  found  that  eight  ounces  a  day  of  breast 
milk  was  insufficient  to  alleviate  the  symptoms  in  a  case 
of  scurvy,  and  that  twelve  ounces  barely  sufficed.  This 
milk  was  from  a  woman  who  was  on  a  liberal  diet  contain- 
ing an  adequate  supply  of  vegetables.  It  had  been  pre- 
viously demonstrated  that  sixteen  ounces  of  cow's  milk 
is  sufficient  to  cure  infantile  scurvy,  so  that  it  is  evident 
that  human  and  cow's  milk  do  not  differ  essentially  in  this 
respect.  There  are,  however,  other  factors  to  be  con- 
sidered— for  example,  the  incomparable  freshness  of  the 
milk  suckled  from  the  breast,  which  may  endow  it  with 
additional  potency,  or  the  possibility  that  the  lack  of 
vitamine  may  be  compensated  for  by  the  large  quantity 
of  milk  consumed.  It  also  may  not  be  entirely  immaterial 
whether  the  vitamine  is  supplied  in  one  dose,  as,  for  exam- 
ple a  daily  feeding  of  orange  or  tomato  juice,  or  whether 
this  factor  is  furnished  to  the  infant  in  frequent  small 
quantities  in  the  mother's  milk  throughout  the  day.  In 
this  connection  we  cannot  help  contrasting  the  relation  of 
beriberi  to  breast  feeding.  As  is  well  known,  infants 
which  develop  beriberi  are  almost  always  nursed  and  not 
bottle-fed,  and  show  signs  of  this  disorder,  although  the 


40  SCURVY:    PAST  AND  PRESENT 

mothers  are  in  apparent  health,  and  give  no  clinical  evi- 
dence of  disease. 

Turning  to  a  consideration  of  the  artificially -fed  infant, 
there  exists  a  somewhat  similar  situation  in  regard  to  the 
occurrence  of  scurvy  on  a  diet  of  raw  cow's  milk.  In 
almost  all  reports  of  this  kind  the  quantitative  viewpoint 
is  entirely  disregarded,  and  little  or  nothing  is  stated  to 
indicate  how  much  milk  the  infant  consumed.  And  yet  this 
factor  is  of  essential  importance  in  interpreting  the  cause 
of  the  nutritional  failure.  It  is  clear,  for  example,  that 
if  a  baby  receives  but  eight  ounces  daily  of  raw  milk — one- 
half  the  requisite  amount — it  may  well  develop  scurvy, 
notwithstanding  the  fact  that  the  milk  has  not  been  heated. 
In  addition  to  the  quantity,  there  are  other  factors  which 
play  a  greater  or  less  role  in  the  relation  of  raw  milk  to  the 
etiology  of  scurvy.  It  is  no  doubt  of  consequence  whether 
the  fodder  of  the  cows  was  rich  or  very  poor  in  the  anti- 
scorbutic factor,  and,  accordingly,  whether  the  baby  re- 
ceived what  may  be  termed  an  "antiscorbutic-rich"  or  an 
"antiscorbutic-poor"  milk.  Furthermore,  the  age  of  the 
milk  must  be  borne  in  mind,  for  we  have  found  that  even 
raw  milk  loses  some  of  its  potency  on  becoming  stale.6 

One  of  the  mooted  questions  relative  to  the  etiology  of 
scurvy  is  the  role  of  heated  milk,  and  more  particularly 
of  pasteurized  millc.  In  view  of  the  vogue  which  pas- 
teurization has  acquired  in  the  large  municipalities,  espe- 
cially in  the  United  States,  this  aspect  has  assumed 
increasing  importance,  and  deserves  detailed  investiga- 
tion. Pasteurization  has  achieved  so  much  in  limiting  the 

6  Moore  raises  the  interesting  question  as  to  whether  a  diseased  condi- 
tion of  the  cow  may  decrease  the  vitamines  of  the  milk — whether  a  certain 
outbreak  of  scurvy  among  guinea-pigs  might  have  been  due  to  their  having 
been  fed  on  the  milk  of  a  cow  suffering  from  experimental  streptococcus 
mastitis.  If  such  proves  to  be  the  case,  it  would  have  an  important  bearing 
on  the  question  of  scurvy  and  pseudo-scorbutic  conditions  in  nursing  infants. 


PATHOGENESIS  AND  ETIOLOGY  41 

infectious  diseases,  especially  the  diarrhceal  disorders  of 
infancy,  that  it  has  come  to  be  looked  upon  as  heresy  to 
deprecate  its  virtues  in  any  regard. 

It  has  become  increasingly  evident  that  in  the  course 
of  pasteurization  milk  loses  an  important  measure  of  anti- 
scorbutic vitamine.  The  term  pasteurization,  when  em- 
ployed in  this  connection,  is  not  meant  to  be  synonymous 
merely  with  the  heating  of  milk  to  140°  to  165°  F.,  but 
embraces  the  entire  commercial  process — the  heating, 
handling,  subsequent  cooling,  aging  and  all  other  factors 
involved.  There  can  be  no  doubt  that  milk  which  has 
undergone  this  elaborate  treatment  has  suffered  in  its  anti- 
scorbutic property.  In  1914  Hess  and  Fish  reported  mild 
cases  of  scurvy  occurring  among  infants  who  had  received 
milk  heated  to  a  temperature  of  165°  F.  for  thirty  minutes. 
This  degree  of  heat  is  claimed  by  many  physicians  and 
hygienists,  including  the  National  Commission  on  Milk 
Standards,  not  to  destroy  its  chemical  constituents. 
Nevertheless  typical  cases  of  scurvy  supervened  after  this 
diet  had  been  followed  for  a  period  of  six  to  nine  months. 
Subsequent  experience,  published  by  Hess  in  1917,  with 
milk  heated  to  only  145°  F.,  served  to  confirm  the  previous 
observations.  That  these  cases  were  true  scurvy  was 
proved  by  the  fact  that  a  cure  resulted  when  raw  milk 
was  substituted.  A  similar  experience  in  Berlin  reported 
by  Neumann  and  others  was  convincing,  but  was  not 
heeded  in  this  country.  In  1901  one  of  the  largest  dairies 
in  that  city  established  a  pasteurizing  plant  where  all 
milk  was  raised  to  a  temperature  of  about  60°  C.  After 
an  interval  of  some  months  infantile  scurvy  began  to  be 
reported  from  various  sources  throughout  the  city.  Neu- 
mann depicts  the  situation  as  follows:  "Whereas,  Heub- 
ner,  Cassel  and  myself  had  seen  only  thirty- two  cases  of 


42  SCURVY:    PAST  AND  PRESENT 

scurry  from  1896  to  1900,  the  number  of  cases  suddenly 
rose  from  the  year  1901,  so  that  the  same  observers — not 
to  mention  a  great  many  others — treated  eighty-three 
cases  in  1901  and  1902."  At  a  spirited  meeting  held  by 
the  Berlin  Medical  Society  in  1903  to  discuss  this  subject, 
Heubner  was  able  to  report  65  cases.  An  investigation 
was  made,  and  the  pasteurization  discontinued.  The  re- 
sult was  almost  immediate,  the  cases  decreasing  just  as 
suddenly  as  they  had  increased.  These  reports  and  others 
demonstrate  that  unless  additional  antiscorbutic  food  is 
given,  a  diet  of  pasteurized  milk  will  lead  to  the  develop- 
ment of  scurvy.  As  the  antiscorbutic  vitamine  is  not 
entirely  destroyed  by  pasteurization,  the  severity  of  the 
disorder  will  be  in  inverse  ratio  to  the  amount  of  milk 
which  is  consumed. 

It  has  been  our  experience  that  milk  pasteurized  in 
the  home  or  institution  did  not  lead  to  scurvy  to  the  same 
extent  as  that  which  was  commercially  pasteurized. 
Babies  fed  onhome-pasteurized  milk  did  not  develop  mani- 
fest scurvy.  The  difference  in  the  two  processes  consists 
mainly  in  the  amount  of  handling  during  the  process  of 
heating  and  the  subsequent  aging  which  the  milk  under- 
goes. An  interval  of  forty-eight  hours  usually  elapses 
between  commercial  pasteurization  and  the  delivery  of 
the  milk  to  the  consumer.  In  New  York  city  most  of  the 
better-grade  milk  is  pasteurized  at  the  farm,  so  that  it  is 
subjected  to  a  longer  period  of  aging  than  the  poorer 
grade,  which  is  not  pasteurized  until  it  reaches  the  city. 
Although  our  results  indicated  the  effect  of  freshness 
or  staleness  on  milk  which  had  been  heated,  they  showed 
also  that  other  factors  must  be  involved,  for  home-pas- 
teurized milk  which  is  forty-eight  hours  old  is  superior 
to  the  commercial  product  of  the  same  age.    This  differ- 


PATHOGENESIS  AND  ETIOLOGY  43 

ence  we  believe  is  due  to  the  handling  which  the  milk 
undergoes,  to  the  mechanical  processes  involved  in  com- 
mercial pasteurization. 

In  considering  this  aspect  of  the  development  of  infan- 
tile scurvy  on  a  diet  of  heated  milk,  it  is  of  interest  to 
refer  to  the  experience  of  Switzerland  and  of  France. 
In  1907  Bernheim-Karrer  reported  nine  cases  of  scurvy 
which  occurred  on  "homogenized"  milk.  This  milk  is 
forced  between  rapidly-rotating  surfaces  at  a  temperature 
of  55°  to  65°  C.  at  a  pressure  of  150  atmospheres.  This 
process  had  been  introduced  the  year  previous  by  a  large 
dairy  which  was  well  known  for  its  excellent  grade  of  milk. 
Before  this  innovation,  milk  usually  had  been  boiled  for 
a  long  while  before  being  fed  to  infants.  In  France  a 
similar  epidemic  of  scurvy  followed  the  introduction  of 
the  use  of  homogenized  milk  (lait  fixe).  Lecornu  gives  an 
interesting  account  of  this  episode,  remarking  on  the  large 
number  of  cases  of  scurvy  occurring  on  this  milk  compared 
with  sterilized  milk,  which  was  employed  so  much  more 
extensively.  These  experiences  furnish  excellent  exam- 
ples of  the  harmful  effect  of  industrial  methods  on  milk, 
especially  on  its  antiscorbutic  vitamine.  Lecornu  also 
emphasized  the  scorbutic  influence  of  "lait  maternise," 
which  is  similar  to  the  German  Gaertner  milk,  and  is  sub- 
jected to  dilution,  centrifugation,  and  sterilization.7  He 
states  that  before  this  preparation  was  introduced  scurvy 
was  practically  unknown  in  France.  Lecornu  attributes 
the  deleterious  effect  of  the  "lait  maternise"  and  the 
"lait  fixe"  to  bacterial  contamination,  as  does  Bernheim- 

7  In  the  case  of  the  "lait  maternise,''  which,  is  a  milk  of  high  fat  con- 
tent, the  dilution  of  the  preparation  also  must  have  been  a  factor.  Ounce  for 
ounce,  cream  is  poorer  in  antiscorbutic  vitamine  than  an  equal  quantity  of 
milk.  It  is  also  possible  that  the  mere  dilution  of  milk — quite  apart  from 
the  absolute  amount  consumed — is  not  immaterial  in  affecting  tbis  highly 
sensitive  vitamine. 


U  SCURVY:    PAST  AND  PRESENT 

Karrer.  We  believe,  rather,  that  its  loss  of  potency 
is  due  to  the  mechanical  processes  to  which  it  has 
been  subjected. 

Boiled  and,  more  particularly,  sterilized  milk,  is  regarded 
as  a  common  cause  of  infantile  scurvy  and  figures  promi- 
nently among  the  foods  held  accountable  for  this  disorder. 
It  has  been  pointed  out,  however,  that  thousands  of  in- 
fants, especially  in  Europe,  receive  milk  of  this  kind,  and 
do  not  develop  scurvy.  Statistics  such  as  those  of  Variot, 
who  has  distributed  in  his  out-patient  department,  during 
a  period  of  twelve  years,  400,000  quarts  of  sterilized  milk 
(heated  in  half -litre  bottles  and  hermetically  sealed  at  the 
farm)  without  observing  a  case  of  scurvy,  must  be 
accorded  weight  in  this  connection.8  Escherich,  some 
years  previously,  stated  that  he  did  not  meet  with  scurvy 
in  Graz,  although  he  was  accustomed  to  feed  babies  on 
sterilized  milk.  Budin,  the  celebrated  French  children's 
specialist,  writes:  "As  for  the  so-called  infantile  scurvy 
which  is  alleged  to  follow  the  use  of  sterilized  milk,  I 
have  heard  a  very  great  deal  about  it  during  the  last  few 
years,  but  I  am  still  looking  for  my  first  case. '  ■  Evidence 
from  such  sources  cannot  be  summarily  cast  aside,  but 
must  be  given  due  consideration.  It  is  evident  that  the 
mere  heating  or  sterilization  of  milk,  although  it  reduces 
the  antiscorbutic  vitamine,  does  not  do  so  to  a  degree 
sufficient  to  lead  to  the  production  of  clinical  scurvy. 
Our  experience  accords  with  that  of  the  above  observers. 
Some  years  ago  we  fed  infants  with  milk  which  had  been 
boiled  for  five  minutes,  and,  at  another  time,  made  use  of 

8  It  is  to  be  noted,  however,  that  Variot  remarks  that  these  infants  fre- 
quently develop  anemia  unless  additional  diet  is  given,  so  that  it  must  be 
considered  open  to  question  whether  some  of  these  babies  did  not  have  latent 
scurvy.  Of  course,  unless  it  is  certain  that  these  infants  were  receiving  only 
sterilized  milk,  and  absolutely  no  other  food,  for  a  period  of  at  least  six 
months,  they  cannot  be  considered  apposite  to  the  question. 


PATHOGENESIS  AND  ETIOLOGY  45 

home-made  evaporated  milk  which  had  been  heated  for  a 
period  of  seventeen  hours,  until  it  had  been  reduced  to 
one-eighth  its  volume.  This  evaporated  milk  was  well 
borne  for  months,  although  slightly  caramelized  in  the 
course  of  heating,  and  did  not  lead  to  any  signs  of  scurvy. 
Clearly  there  are  other  factors  involved  in  this  question 
besides  the  mere  subjection  to  heat.  We  believe  that  every 
step  in  the  process  is  important — the  freshness  of  the 
milk,  whether  or  not  it  is  agitated  and  exposed  to  the 
air,  whether  it  is  sealed  carefully  and  used  soon  after  ster- 
ilization,9 and,  finally,  whether  the  baby  receives  a  suffi- 
cient quantity.  If  this  milk,  which  has  certainly  lost  some 
of  its  vitamine  content,  is  given  in  small  amount,  it  will  not 
supply  an  adequate  amount  of  the  antiscorbutic  factor. 

Neumann,  Czerny,and  others  state  that  they  have  even 
cured  infantile  scurvy  by  giving  boiled  milk  obtained  from 
a  different  source.  In  the  Berlin  epidemic,  Neumann  laid 
particular  emphasis  on  the  fact  that  the  milk  which  in- 
duced scurvy  had  been  doubly  heated,  having  been  pas- 
teurized commercially  and  later  boiled  in  the  home  before 
it  was  fed  to  the  baby.  Plantenga  has  also  laid  stress  on 
the  influence  of  tivo-fold  heating,  citing  an  interesting 
experience  with  scurvy  in  his  clinic.  "When  the  milk  was 
pasteurized  one  day  and  boiled  for  five  minutes  on  the 
subsequent  morning,  23  cases  of  infantile  scurvy  de- 
veloped among  the  200  infants  attending  his  dispensary. 
The  following  year  when  the  procedure  was  altered  so 
that  the  milk  was  merely  pasteurized,  no  case  of  this  dis- 
order developed.    There  can  be  no  doubt  that  milk  which 

8  Carel  reports  an  interesting  case  which  points  to  the  importance  of 
stalcness.  A  baby  was  taken  to  the  country  with  a  supply  of  sterilized  milk 
sufficient  to  last  for  some  weeks.  At  the  end  of  this  time  it  did  not  thrive, 
but  regained  its  health  when  a  fresh  supply  of  milk  was  used.  When  this 
second  supply  became  stale  the  infant  again  developed  the  same  signs,  and 
the  condition  was  diagnosed  as  scurvy. 


46  SCURVY:    PAST  AND  PRESENT 

has  been  heated  twice  must  have  lost  more  of  its  antiscor- 
butic properties  than  milk  which  has  been  heated  but  once, 
and  that  aging  also  must  contribute  to  this  loss.  "Whether 
there  is  what  may  be  termed  a  peculiar  sensitization  of 
milk  following  pasteurization,  has  not  been  defi- 
nitely shown. 

Up  to  the  present  time  dried  milk  has  played  an 
insignificant  role  in  the  etiology  of  infantile  scurvy.  One 
of  the  factors  which  has  hindered  the  general  acceptance 
of  dried  milk  by  physicians  and  laymen  has  been  the  fear 
that  its  use  might  lead  to  .the  development  of  Barlow's 
disease.  It  is  therefore  important  to  consider  this  aspect 
of  the  subject,  especially  as  dried  milk  seems  destined  to  be 
used  to  an  increasing  extent.  A  recent  report  to  the  Local 
Government  Board  by  Coutts  states  that  "Millard  and 
Naisch  in  England  confirmed  the  testimony  of  Miele  in 
Belgium,  and  Gautier  and  Genevoix  in  France,  that  scurvy 
is  not  to  be  feared' '  from  this  foodstuff.  This  coincides 
with  our  experience,  namely,  that  dried  milk  not  only  does 
not  lead  to  scurvy,  but  may  contain  sufficient  antiscor- 
butic vitamine  to  cure  this  disorder.  Recently  a  scorbutic 
baby  was  fed  with  milk  which  had  been  dried  by  the  so- 
called  Just-Hatmaker  process — whereby  it  is  subjected 
on  a  drum  for  a  few  seconds  to  about  230°  F. — with  the 
result  that  the  hemorrhages  of  the  gums  began  to  be 
absorbed  in  about  three  days,  and  all  symptoms  to  dis- 
appear shortly  thereafter.  This  infant  received  dried 
milk  to  the  equivalent  of  24  ounces  of  fresh  milk,  and 
this  preparation  had  been  dried  and  canned  somewhat 
over  three  months  before  it  was  used.  Recently  two  in- 
fants, suffering  from  marked  scurvy,  were  treated  with 
milk  which  had  been  dried  six  months  previously.  The 
one  received  only  sixteen  ounces  a  day  and  the  other  a 


PATHOGENESIS  AND  ETIOLOGY  47 

quart;  both  recovered  within  a  few  days  after  this  food 
had  been  substituted  for  malt  soup.  Not  long  ago, 
as  reported  elsewhere  in  a  paper  by  Unger  and  myself, 
after  curing  a  baby  of  scurvy  by  means  of  this 
milk,  it  was  maintained  in  health  for  a  subsequent 
period  of  three  months  on  a  diet  which  contained 
no  additional  source  of  antiscorbutic  vitamine.  These 
results  are  emphasized  as  illustrating  the  peculiar 
relationship  of  drying  and  of  the  application  of  heat  to 
the  antiscorbutic  vitamine,  and  because  recently  several 
reports  have  appeared,  for  example,  that  of  Barnes  and 
Hume  in  England,  and  of  Hart,  Steenbock  and  Smith  in 
this  country,  to  the  effect  that  dried  milk  is  devoid  of  anti- 
scorbutic value.  The  difference  of  opinion  is  due  to  the 
assumption  that  dried  milk  is  a  uniform  product  and  has 
identical  antiscorbutic  properties.  For  milk  to  retain 
its  antiscorbutic  value,  notwithstanding  drying,  it  must 
have  been  rich  in  vitamine  before  desiccation,  it  must 
have  been  dried  quickly,  and  packed  within  the  shortest 
possible  interval  in  air-tight,  preferably  hermetically- 
sealed,  containers.  As  in  relation  to  the  heating  of  milk, 
so  in  regard  to  its  drying,  it  is  not  the  degree  of  heat  to 
which  it  is  subjected  which  is  all  important,  but  rather 
the  associated  conditions.  The  merits  of  each  process  will 
have  to  be  tested  individually  and  perhaps  even  each  par- 
ticular brand  of  milk.10 

In  the  foregoing,  the  dictum  has  been  accepted  without 
comment  that  fresh  milk  may  be  either  rich  or  poor  in 
antiscorbutic  vitamine.    This  point  of  view  has  recently 

10  In  making  tests  of  dried  milk  particular  attention  should  be  paid  to 
the  age  of  the  milk  before  it  is  desiccated.  Investigators  should  also  be  cer- 
tain that  the  milk  has  not  undergone  heating  previous  to  the  drying  process. 
Some  well-known  brands  of  dry  milk  have  been  not  only  pasteurized,  but 
subsequently  evaporated  before  drying. 


48  SCURVY:    PAST  AND  PRESENT 

gained  general  acceptance,  on  the  assumption  that  the 
milk  of  the  stall-fed  cow  is  markedly  deficient  in  this  fac- 
tor. Kecent  work  by  Hart,  Steenbock  and  Ellis  gives  evi- 
dence that  "summer  pasture  milk  is  much  richer  in  this 
nutritive  factor  than  dry  feed  milk  or  winter  produced 
milk,  involving  the  use  in  the  ration  of  corn  silage  or 
sugar  mangels. ' '  In  some  experiments  (unpublished)  we 
have  found  that  dried  milk  shows  similar  variations,  being 
a  much  more  potent  antiscorbutic  when  obtained  from 
cows  fed  on  fresh  fodder  than  a  similar  milk  from  the 
same  cows  on  fodder  containing  a  minimum  amount  of 
antiscorbutic  vitamine.  The  supposition  of  a  direct  quan- 
titative ratio  between  the  antiscorbutic  intake  in  the  food 
and  output  in  the  milk  needs  confirmation,  especially  as  it 
does  not  quite  coincide  with  the  experience  among  human 
beings  in  countries  where  adult  scurvy  is  endemic.  In  such 
countries — for  example,  Russia — nursing  infants  do  not 
develop  scurvy  to  the  extent  that  would  be  expected,  and  it 
is  possible  that  this  exemption  is  due  in  part  to  a  selective 
secretion  of  antiscorbutic  vitamine  into  the  milk. 

As  is  well  known,  a  diet  of  condensed  milk  leads  to 
scurvy.  This  is  not  surprising,  considering  the  prolonged 
heating  to  which  this  milk  has  been  subjected.  It  is  prob- 
able that  many  cases  of  mild  scurvy  developing  on  this 
food  and  characterized  by  beading  of  the  ribs  (rosary) 
and  other  indefinite  manifestations,  have  been  erroneously 
diagnosed  as  rickets. 

It  is  hardly  necessary  to  discuss  separately  the  various 
kinds  of  milk  which  have  led  to  scurvy  in  the  course  of 
infant  feeding.11     The  principles  laid  down  in  the  pre- 

"Ausset  reports  a  definite  case  of  scurvy  developing  in  a  baby  nine 
months  old,  which  had  received  buttermilk  almost  since  birth.  At  the  time 
of  admission  to  the  hospital  it  was  petting  900  c.c.  a  day.  This  case  is  inter- 
esting on  account  of  the  acid  nature  of  the  food. 


PATHOGENESIS  AND  ETIOLOGY  49 

ceding  discussion  hold  good  for  milk  of  all  kinds.  Heat 
will  destroy  a  certain  amount  of  vitamine,  and,  if  the  heat- 
ing is  followed  by  aging,  still  more  will  be  lost.  If  an 
interval  elapses  and  a  second  heating  ensues,  there  will 
be  further  loss  of  vitamine.  it  should  never  be  forgotten 
in  considering  foods  in  their  relation  to  the  causation  of 
scurvy,  that  the  amount  of  food  given  must  not  be  over- 
looked. For  example,  a  pint  of  ordinary  pasteurized  milk 
will  lead  to  scurvy,  whereas  a  quart  in  most  cases  will  be 
sufficient  to  tide  the  baby  over  until  the  period  of  mixed 
feeding.  No  general  rule  can  be  laid  down,  however,  as 
may  be  judged  from  the  fact  that  dried  milk  which  has 
been  subjected  to  almost  all  the  influences  which  are  dele- 
terious to  the  antiscorbutic  vitamine — heating,  drying, 
aging,  all  carried  out  in  a  neutral  medium — nevertheless 
retains  its  specific  potency. 

Infantile  scurvy  has  always  been  far  more  prevalent 
in  England  and  in  America  than  in  Europe,  notwithstand- 
ing the  fact  that  on  the  continent  practically  all  milk  for 
babies  is  boiled  or  sterilized.  This  has  been  ascribed,  and 
probably  rightly  so,  to  the  widespread  usage  of  proprie- 
tary foods  in  the  English-speaking  countries.  Among 
the  cases  reported  by  the  American  Pediatric  Society 
about  60  per  cent,  had  been  given  foods  of  this  description. 
How  is  this  relationship  to  be  explained?  These  prepara- 
tions in  general  may  be  stated  to  consist  of  cereals,  sugar, 
with  occasionally  a  small  amount  of  dried  milk ;  they  are 
mixed  with  varying  proportions  of  water  and  milk  and 
then  cooked.  It  is  evident  that  two  important  causative 
factors  of  scurvy  are  thus  furnished,  namely,  a  small  and 
inadequate  quota  of  milk  and  the  application  of  heat.  In 
most  instances  not  more  than  sixteen  to  twenty  ounces 
of  milk  are  used  to  make  up  the  day's  feeding,  and  fre- 

4 


50  SCURVY:    PAST  AND  PRESENT 

quently  this  has  been  previously  pasteurized.  But  there 
is  an  additional  factor  which  comes  into  play  in  this  con- 
nection, one  to  which  we  have  recently  drawn  attention 
in  treating  of  ' '  The  Deleterious  Effect  of  the  Alkalrzation 
of  Infants'  Food."  It  has  been  shown  that  the  antiscor- 
butic vitamine  is  peculiarly  sensitive  to  the  faintest  alka- 
line reaction,  in  which  medium  it  rapidly  undergoes 
deterioration,  and  even  total  destruction  if  heat  is  applied. 
Proprietary  foods,  with  but  few  exceptions,  are  alkaline, 
having  been  rendered  so  by  the  addition  of  potassium 
carbonate  or  bicarbonate,  in  order  to  prevent  acid  fer- 
mentation of  the  fat  and  to  counterbalance  the  relative 
poverty  of  potassium  in  cow's  milk.  Little  or  no  regard 
has  been  paid  to  this  reaction ;  the  text-books  on  children's 
diseases  give  this  point  no  consideration  whatsoever,  ex- 
pressing the  salt  content  merely  in  terms  of  total  ash. 
By  this  means  ideal  conditions  are  furnished  for  the 
destruction  of  a  large  part  of  the  vitamine,  and  if  this 
factor  is  not  present  in  excess,  scurvy  will  readily  develop. 
It  is  to  these  various  circumstances — the  deficiency  of 
milk,  the  alkalinity  and  the  heating — that  the  scorbutic 
quality  of  proprietary  foods  is  to  be  ascribed. 

The  most  flagrant  example  of  an  infant 's  food  leading 
to  scurvy  is  "malt  soup" — an  alkaline  preparation  of 
malt,  which  is  prepared  with  flour  and  a  small  amount  of 
milk.12  This  food  brings  about  scurvy  almost  invariably 
unless  an  antiscorbutic  is  added  to  the  dietary.  That  this 
effect  is  due  to  the  alkaline  potassium  carbonate  was 
shown  by  a  recent  test  which  is  illustrated  in  chart. 
(Fig.  2).    Here  we  see  that  in  a  case  of  scurvy,  when  the 

"Malt  soup  is  prepared  by  dissolving  the  alkaline  malt  soup  extract  in 
water,  and  mixing  wheat  flour  with  milk.  These  two  mixtures  are  then 
boiled  together  for  about  three  minutes.  According  to  some  directions,  11 
ounces  of  milk  are  used;  in  our  formula  16  ounces  were  employed. 


PATHOGENESIS  AND  ETIOLOGY 


51 


food  was  altered  and  prepared  with  the  same  amount  of 
milk  and  alkali,  the  disorder  did  not  abate  (although  the 
carbohydrate  had  been  discontinued),  but  when  the  potas- 
sium carbonate  was  omitted  a  gain  in  weight  ensued,  and, 
we  may  add,  the  symptoms  disappeared. 

A  test  of  this  kind  once  more  raises  the  question 
whether  carbohydrates  lead  to  the  development  of  scurvy. 
As  previously  stated,  there  are  many  who  believe  that  the 
carbohydrates,  especially  starch,  have  this  harmful  effect 


Lbs. 
"  19 

18- 

Penodl 
Malt  Soup 
'Containing  IboZ-MUV; 

\dOHA  P/rh  f.a rhnna  +  o  \_. 

.  Period.  Z 

-16  n-7    Mil" 

- 

-     ~Pp  r  i  or\   *\ 

I  JLTld   Pot 
ClTbOTIiVi 

lo  oz.  MHk 

without 

p 

** 

i_ 

-  Pot.  Carbonate  ■ 

i 

,' 

/ 

'  | 

1 

s 

L 

_i 

y 

s 

/ 

_ 

/ 

/ 

\ 

L 

_s 

/ 

/ 

J_ 

s 

Fia.  2. — Human  Bcuryy:  weight  curve  of  a  baby  that  developed  scurvy  on  a  diet  of  malt 
soup  (period  1).  During  period  2  the  flour  and  malt  soup  were  omitted  from  the  diet,  the 
same  amount  of  milk  and  potassium  carbonate  being  continued.  The  disorder  did  not  abate. 
The  only  change  in  period  3  was  a  discontinuation  of  the  potassium  carbonate.  This  brought 
about  a  gain  in  weight  and  cure,  showing  the  destructive  effect  of  the  alkali  on  the  vitamine. 

by  requiring  a  large  amount  of  the  various  vitamines  for 
their  metabolism.  This  relationship  was  first  brought 
forward  by  Bradden  and  Cooper  in  regard  to  beriberi.  It 
is  a  suggestion  which  cannot  be  disregarded  in  view  of 
the  great  amount  of  scurvy  which  comes  about  on  diets 
rich  in  carbohydrates,  especially  those  containing  malt 
sugar.  We  do  not  believe,  however,  that  the  harmful 
effect  which  this  foodstuff  exerts  can  be  explained  on  the 
above  hypothesis,  as  experience  has  shown  that  infants 
may  receive  for  many  months  equally  large  amounts  of 
carbohydrates — cane  sugar,  flour,  or  a  combination  of 
both — and  nevertheless  not  manifest  a  similar  tendency  to 
develop  scurvy. 

Age  Incidence. — Scurvy  may  occur  at  any  age  if  the 


52  SCURVY:    PAST  AND  PRESENT 

diet  does  not  furnish  sufficient  antiscorbutic  factors.  As 
a  matter  of  fact,  it  is  encountered  most  often  among  in- 
fants and  adults,  not  because  these  two  age-groups  are 
particularly  susceptible,  but  because  there  are  peculiar 
attendant  circumstances.  In  the  case  of  the  infant,  it  is 
due  to  the  fact  that  for  almost  the  entire  first  year  of  its 
life  it  is  dependent  entirely  upon  milk,  a  foodstuff  poor  in 
antiscorbutic  vitamine,  and  containing,  under  favorable 
conditions,  barely  enough  to  meet  its  requirement.  If, 
therefore,  the  potency  of  the  milk  is  weakened,  or  if  an 
insufficient  quantity  is  fed,  and  more  particularly  when 
both  of  these  factors  are  involved,  a  scorbutic  condition 
will  ensue.  The  reason  why  older  children,  those  over 
one  and  a  half  or  two  years  of  age,. do  not  develop  scurvy 
is  largely  due  to  their  varied  and  liberal  diet,  which  is 
amply  provided  by  the  mother  or  guardian,  so  that  even 
in  times  of  want  they  receive  more  than  their  due  share 
of  the  available  food  supply.13 

From  a  clinical  standpoint  scurvy  may  be  said  to  occur 
in  infants  during  the  second  half  year  of  their  lives.  There 
is  general  agreement  on  this  point;  it  is  borne  out  by  the 
investigation  of  the  American  Pediatric  Society  and  by 
the  statistics  of  various  individuals.  On  the  basis  of  a 
large  experience,  Still  states  that  nearly  eighty  per  cent, 
of  the  cases  appearbetween  the  ages  of  six  and  ten  months, 

13  It  would  seem,  however,  that  the  growing  infant  requires  relatively 
more  antiscorbutic  vitamine  than  does  the  adult.  We  know  that  its 
caloric  requirement  is  fully  a  quarter  to  a  third  greater.  In  regard  to  vita- 
mine, judgment  cannot  be  based  on  experimental  evidence,  but  on  compara- 
tive figures.  For  example,  unless  we  take  this  viewpoint,  we  must  believe 
that,  as  an  infant  of  six  months  weighing  15  pounds  requires  15  c.c.  of 
orange  juice  daily  to  furnish  its  antiscorbutic  quota,  an  adult  weighing  160 
pounds  requires  180  c.c.  daily — the  juice  of  three  good-sized  oranges.  On 
this  basis  the  adult  would  require  six  quarts  (6000  c.c.)  of  fresh  milk 
daily,  twelve  times  the  minimum  requirement  for  an  infant,  which  is  one 
pint  (500  c.c.)  a  day.    These  figures  are  manifestly  too  high. 


PATHOGENESIS  AND  ETIOLOGY  53 

and  that  in  no  case  did  the  disorder  occur  before  the  age 
of  five  months.  It  is  of  importance  from  both  the  etio- 
logic  and  the  therapeutic  standpoint  to  distinguish  clearly 
between  the  age  when  infantile  scurvy  is  commonly  diag- 
nosed, and  the  earlier  stage  when  it  appears  as  a  general 
nutritional  disorder.  We  must  remember  that  scurvy  gen- 
erally takes  from  six  to  nine  months  to  become  manifest, 
this  developmental  period  varying  mainly  in  proportion 
to  the  degree  of  the  dietary  deficiency.  It  is  evident, 
therefore,  that  there  must  be  a  prolonged  period  of  nutri- 
tional failure  which  precedes  the  diagnosis.  This  stage 
consists  of  two  early  phases,  the  first  months  where  the 
faulty  diet  causes  no  apparent  change  and  seems  to  have 
no  deleterious  effect  on  the  infant,  and  the  second,  of 
latent  and  subacute  scurvy.  The  "latent"  condition  is 
one  merely  of  unsatisfactory  nutrition  and  retarded 
growth,  which  it  is  not  possible  to  interpret;  "subacute 
scurvy,"  which  develops  subsequently,  is  distinguished 
by  characteristic  signs  and  symptoms.  We  shall  not  re- 
view their  symptomatology,  as  it  is  given  in  the  chapter 
devoted  to  this  topic.  The  subject  is  brought  forward  in 
this  connection  to  emphasize  the  fact  that  the  scorbutic 
condition  occurs  far  earlier  than  is  generally  realized, 
and  furthermore,  that  if  the  earlier  and  more  subtle  symp- 
toms of  scurvy  were  comprehended,  the  age  incidence 
would  fall  earlier  than  the  current  figures  indicate.  The 
earliest  instance  of  this  disorder  which  we  have  seen 
occurred  in  a  baby  four  and  a  half  months  of  age. 

Age  does  not  seem  to  play  a  definite  role  in  regard 
to  the  incidence  among  adults.  Scurvy  frequently  has 
been  encountered  among  old  men,  and  is  of  common  occur- 
rence among  the  most  vigorous  of  the  nation,  the  young 
soldiers  and  sailors.    Some  have  stated  that  it  takes  place 


54  SCURVY:    PAST  AND  PRESENT 

less  often  among  soldiers  in  the  twenties  than  among 
those  in  the  thirties,  but  this  has  not  been  demonstrated. 
The  fewest  cases  have  been  reported  among  children  over 
two  years  of  age.  It  was  due  to  the  apparent  immunity 
of  this  age-group  that,  until  very  recently,  German  writers 
doubted  the  identity  of  infantile  and  adult  scurvy.  The 
exclusion  of  children  of  this  age  is  merely  fortuitous  and, 
moreover,  is  by  no  means  absolute.  One  of  the  earliest 
cases  of  scurvy  in  children,  reported  by  Montfalcon, 
occurred  in  a  child  six  years  old.  Bateman  in  America 
described  a  case  in  a  child  of  about  this  age.  Barlow, 
in  one  of  his  first  articles,  reported  scurvy  in  a  small 
group  of  older  children.  The  case  so  frequently  quoted 
by  German  authors  in  this  connection  is  that  of  Fraenkel, 
who  described  both  clinically  and  pathologically  a  case  of 
scurvy  in  a  boy  eight  years  of  age.  These  cases  by  no 
means  exhaust  the  number  which  are  reported.  Recently, 
Tobler  has  given  us  an  account  of  scurvy,  occurring  during 
the  war,  in  a  Viennese  foundling  asylum  which  harbored 
children  between  the  ages  of  two  and  fourteen. 

Season  and  Climate. — Many  of  the  older  writers  laid 
great  stress  on  the  influence  of  season  on  the  occurrence 
of  scurvy,  which  they  believed  broke  out  particularly  in 
the  cold  and  damp  months  of  the  fall,  winter  and  early 
spring.  It  is  true  that  most  of  the  epidemics  have  occurred 
at  these  seasons  of  the  year.  This  is  merely  what  should 
be  expected,  considering  that  the  disease  depends  mainly 
upon  the  supply  of  fresh  fruits  and  vegetables.  Where 
conditions  are  abnormal,  as  in  war,  there  have  been  nota- 
ble exceptions  to  this  seasonal  incidence.  In  the  "Report 
of  the  War  of  the  Rebellion "  there  is  an  instructive 
graph  illustrating  the  occurrence  of  scurvy  in  our  Civil 
War  and  in  the  Crimean  War,  which  shows  that  this 


PATHOGENESIS  AND  ETIOLOGY  55 

disease  prevailed  to  the  greatest  extent  during  the  winter 
months  in  the  former,  whereas  in  Crimea,  the  season  of 
greatest  frequency  was  the  summer  time.  One  of  the 
severest  outbreaks  of  scurvy  on  record  is  that  which 
occurred  at  the  siege  of  Thorn  in  Germany  in  the  year 
1703.  During  the  months  of  July  and  August,  when  the 
weather  was  excessively  hot,  scurvy  ravaged  the  be- 
sieged army.  There  are,  furthermore,  many  reports  of 
scurvy  in  the  tropics  during  the  dry  season.  In  the 
island  of  Aruba,  in  the  Dutch  West  Indies,  which  has 
been  visited  by  scurvy  year  after  year,  and  which  is 
referred  to  elsewhere,  the  disease  is  endemic  during  the 
dry,  hot  season.  Formerly  it  broke  out  on  the  men-of- 
war  and  vessels  of  the  mercantile  marine  while  they  were 
in  southern  waters.  As  regards  infantile  scurvy,  it  has 
always  seemed  to  us  that  season  played  a  slight  role ;  that 
cases  which  occurred  in  the  summer  tended  to  be  less 
severe  and  to  be  characterized  by  periods  of  intermission 
rarely  observed  in  the  winter  time. 

The  effect  of  climate  has  been  accorded  a  variable  place 
in  the  etiology  of  scurvy.  Lind  believed  that  a  damp,  cold 
climate,  such  as  that  of  the  Low  Countries,  was  conducive 
to  scurvy.  On  the  other  hand,  since  it  is  realized  that  diet 
is  the  essential  element,  all  other  factors  have  been 
regarded  as  of  no  moment  whatsoever.  It  is  difficult  to 
pass  judgment  on  this  question,  since  scurvy  is  now  en- 
demic in  such  a  limited  area  of  the  world.  It  seems  quite 
possible  that  a  damp,  cold  climate,  which  depresses  the 
various  functions  of  the  body,  may  exert  an  influence 
where  the  quota  of  antiscorbutic  foodstuff  is  not  quite 
adequate.  Exposure  to  infection  is  also  greater  under 
such  climatic  conditions. 


56  SCURVY:    PAST  AND  PRESENT 

Economic  status  has  to  be  considered  in  connection  with 
infantile  scurvy.  Numerous  writers  have  drawn  atten- 
tion to  the  fact  that  scurvy  is  seen  relatively  more  fre- 
quently among  the  infants  of  the  well-to-do  and  the  rich 
than  among  those  of  the  poor.  This  curious  and  para- 
doxical situation  is  due  to  the  zealous  care  which  the 
former  receive — the  extreme  precautions  in  sterilizing 
the  milk,  the  addition  to  the  formulas  of  expensive  pro- 
prietary foods,  the  watchfulness  to  avoid  the  child's  ob- 
taining a  chance  bit  of  fruit  or  vegetable.  Since  the 
popularization  of  commercially-pasteurized  milk  in  the 
larger  municipalities,  and  the  advertising  propaganda 
for  the  sale  of  "baby  foods"  which  has  extended  their  use 
among  the  masses,  this  distinction  in  the  social  status  has 
been  largely  obliterated. 

Sex  seems  to  play  no  part  in  the  etiology  of  scurvy. 
Several  writers  have  claimed,  however,  that  there  is  a 
certain  degree  of  racial  immunity.  For  example,  Shep- 
pard  reports  that  the  Zhob  Kakai  seldom  develops  scurvy, 
although  he  naturally  excludes  vegetables  from  his  diet, 
and  Boerich  noted  among  the  prisoners  of  war  that  the 
Slavs,  especially  the  "White  Russians,  were  more  sus- 
ceptible.14 Of  course  a  lack  of  susceptibility  of  this 
nature  can  be  merely  relative.  Such  a  racial  distinction 
may  seem  far-fetched,  but  if  we  admit  that  disposition  and 
habits  of  life  can  play  a  role,  it  is  quite  possible  for  races 
to  vary  in  their  predisposition  to  this  disorder.  Moreover, 
we  shall  see  that  individuals  differ  markedly  in  this  re- 
spect.   Lind  and  others  repeatedly  emphasize  the  fact  that 

14  It  would  be  of  interest  to  know  whether  the  negro  infant  is  more  sus- 
ceptible than  the  white  baby,  in  view  of  its  markedly  heightened  suscep- 
tibility to  rickets.  There  are,  however,  no  reports  or  statistics  to  enlighten 
us  on  this  point. 


PATHOGENESIS  AND  ETIOLOGY  57 

the  indolent  and  slothful  sailor  was  stricken  with  scurvy- 
far  oftener  than  the  one  who  was  active,  and  claimed 
that  physical  exercise  even  tended  to  bring  about  a  cure.15 
Those  who  have  had  a  large  experience  with  scurvy  in 
adults  are  almost  unanimous  in  believing  that  a  psychic 
element  enters  into  its  etiology.  In  this  way,  in  a  measure, 
they  account  for  the  frequency  of  scurvy  among  defeated 
troops,  in  besieged  armies,  and  among  men  depressed  by 
homesickness,  fatigue,  and  discouragement.  This  point  of 
view  cannot  be  lightly  disregarded,  bearing  in  mind  that 
depressed  mental  states  alter  the  functions  of  the  organs 
and  markedly  affect  secretion.  The  many  cases  and  epi- 
demics in  institutions  for  the  insane  cannot,  however,  be 
attributed  to  this  cause,  but  are  probably  almost  entirely 
due  to  a  want  of  supervision  of  the  dietary.  Among  in- 
fants, the  question  of  the  influence  of  race  and  of  the 
mental  state  needs  but  little  consideration.16  For  some 
time  we  have  carefully  observed  the  course  of  scurvy 
among  happy  and  contented  infants  compared  with  those 
of  an  unhappy  and  fretful  disposition ;  in  some  instances 
the  former,  although  the  diet  was  similar,  seemed  to  de- 
velop scurvy  less  readily  than  the  latter. 

There  can  be  no  doubt  that  there  is  predisposition  to 
scurvy,  as  there  is,  probably,  to  every  nutritional  dis- 
order. Among  soldiers  and  sailors  a  certain  number 
develop  scurvy  on  the  same  ration  which  does  not  harm 
others.     Some  years  ago  when  scurvy  developed  among 

15 "  Where  the  indisposition  is  but  beginning,  and  even  when  the 
gums  have  been  pretty  much  tainted,  there  have  been  numerous  instances  of 
a  perfect  recovery  without  having  the  benefit  of  fresh  vegetables ;  provided 

the  patient  is  able  to  use  due  exercise When  it  is  advanced  to  what 

I  have  called  the  second  stage  it  is  hardly  to  be  cured  without  their  (fruits 
and  vegetables)   assistance."     (Lind. ) 

"CaillG  has  described  a  case  of  scurvy  in  an  infant  suffering  from  Mon- 
golian idiocy,  and  we  have  also  seen  a  similar  case. 


58  SCURVY:    PAST  AND  PRESENT 

a  group  of  infants  fed  on  pasteurized  milk,  this  idiosyn- 
crasy was  noted.  The  distinction,  however,  is  rarely 
sharply  denned.  Careful  clinical  investigation  will  gener- 
ally show  that  the  infants  which  seem  to  be  spared  are 
not  thriving  quite  normally;  they  are  somewhat  pale, 
and  do  not  gain  in  weight  as  they  should,  and  their  appetite 
is  poor.  The  most  interesting  experience  of  this  kind  is 
the  following  which  is  frequently  cited :  In  a  family  where 
the  first  child  developed  scurvy,  Finkelstein  took  the 
precaution,  in  the  case  of  the  second  child,  to  have  the 
milk  boiled  for  as  short  a  time  as  possible,  and  to  begin 
mixed  feeding  early.  In  spite  of  these  precautions  this 
boy  also  developed  scurvy.  Finkelstein  states  that  once 
before  he  had  met  with  a  similar  mishap.  An  experience 
which  he  relates,  regarding  a  foster-mother,  an  excellent 
nurse,  who  had  three  infants  in  succession  develop  scurvy 
in  spite  of  preventive  measures,  is  also  of  interest  in  this 
connection.  The  latter  occurrence  evidently  cannot  be 
attributed  to  hereditary  or  family  predisposition,  and 
serves  to  emphasize  the  inherent  difficulties  of  the  subject, 
v.  Starck's  report  of  an  instance  where  twins  were  fed 
on  similar  milk  mixtures  and  one  developed  scurvy, 
whereas  the  other  thrived  satisfactorily,  is  a  striking 
illustration  of  the  role  of  idiosyncrasy.  This  case,  as 
well  as  many  others,  fails  to  be  absolutely  convincing 
in  view  of  the  fact  that  the  daily  intake  of  milk  is 
not  recorded. 

A  predisposition  to  scurvy  cannot  be  ascribed  to  a 
condition  of  general  malnutrition.  For  example,  among 
infants  it  has  never  seemed  that  those  suffering  from 
marasmus  or  atrophy  were  particularly  prone  to  develop 
scurvy.    "Whether  syphilis,  tuberculosis  or  malaria  tends 


PATHOGENESIS  AND  ETIOLOGY  59 

to  precipitate  the  onset  of  this  disorder  cannot  be  stated.17 
In  view  of  the  fact  that  prematurity  is  such  an  important 
factor  in  the  pathogenesis  of  rickets,  it  would  be  of  interest 
to  know  whether  a  similar  relationship  exists  between 
infantile  scurvy  and  prematurity.  The  only  clinical  con- 
dition which  we  have  found  predisposing  to  scurvy  is  the 
' '  exudative  diathesis ' '  of  Czerny,  a  term  which  implies  a 
tendency  to  develop  exudations  of  the  skin  or  of  the 
mucous  membranes.  Probably  it  is  not  without  signifi- 
cance that  in  this  diathesis  the  blood-vessels  may  evince 
a  decided  weakness,  an  increased  permeability,  as  demon- 
strated by  the  "capillary  resistance  test."  (See 
Symptomatology. ) 

Nothing  whatsoever  is  known  regarding  the  possible 
influence  of  the  fat,  protein,  carbohydrate  and  salt  content 
of  the  diet  on  the  development  of  scurvy.  Is  it  entirely 
immaterial  whether  one  or  another  food  element  largely 
predominates,  or  is  the  antiscorbutic  factor  to  some  extent 
modified  by  other  components  of  the  food?  Influences 
of  this  kind,  which  at  most  are  secondary,  cannot  be 
ascertained  by  the  biologic  test  which  at  present  has  to 
be  relied  on  to  measure  the  development  of  scurvy  and  the 
potency  of  antiscorbutics.  It  is  quite  possible  that  the 
course  of  scurvy  may  be  affected  by  the  character  of 
gastric  and  intestinal  digestion,  by  the  activity  of  the 
glands  which  pour  their  secretions  into  these  organs,  by 
the  destruction  or  elimination  of  the  antiscorbutic  factor 
in  the  food.  The  frequent  association  of  dysentery  and 
scurvy  noted  during  the  recent  war  and  referred  to  by 
many  previous  writers,  shows  the  effect  of  intestinal  dis- 
orders.    These  hypotheses  are  tentatively  advanced  be- 

17  Many  of  the  older  authors  believed  that  mercurial  drugs  were  espe- 
cially prejudicial  in  cases  of  scurvy. 


60  SCURVY:    PAST  AND  PRESENT 

cause  it  is  evident  that  some  factor  exists,  apart  from  the 
mere  antiscorbutic  value  of  the  diet,  which  at  times  exerts 
a  potent  influence  on  the  development  of  scurvy.  Cases 
developing  in  spite  of  a  moderate  amount  of  antiscorbutic 
food,  and  others  not  responding  to  the  addition  of  vege- 
tables or  fruit  to  the  diet — although  not  numerous — have 
occurred  too  frequently  and  have  been  reported  by  too 
experienced  observers  to  be  brusquely  disregarded.  For 
example,  Neumann,  one  of  the  keenest  clinical  students  of 
scurvy,  stated  that  he  had  met  with  four  instances  of  this 
nature.  Hess  and  Fish  reported  two  similar  experiences. 
The  secondary  etiologic  factors  are  mainly  predispos- 
ing; a  few  words,  however,  must  be  added  concerning 
what  may  be  termed  exciting  factors.  Infection  is  the 
most  important  condition  which  may  suddenly  and  pre- 
cipitously induce  scurvy.  This  fact  was  brought  to  our 
attention  in  1912  in  connection  with  the  outbreak  of  scurvy 
among  infants  receiving  pasteurized  milk.  Its  explana- 
tion was  not  clear  at  the  time,  but  was  elucidated  by  subse- 
quent experience,  and  was  described  in  1917  as  follows : 
"  Latent  scurvy  was  prematurely  changed  to  florid  scurvy 
by  the  presence  of  a  ward  infection;  an  epidemic  of 
1  grippe'  precipitated  an  epidemic  of  scurvy  exceptional 
in  its  hemorrhagic  tendency.' '  The  association  of  scurvy 
and  infection  has  been  recently  emphasized  by  McCarrison 
and  others,  and  seems  to  hold  good  for  the  other  so-called 
deficiency  diseases.  In  this  connection  one  other  exciting 
cause  of  scurvy  may  be  mentioned,  namely,  trauma.  The 
older  writers  noticed  that  following  a  fall  or  an  accident, 
a  sailor  frequently  developed  scurvy,  and  Barlow  in  1894 
remarked  on  the  influence  of  trauma  in  connection  with 
infantile  scurvy.  As  might  be  inferred,  its  effect  is  mainly 
to  induce  premature  rupture  of  the  weakened  blood-ves- 


PATHOGENESIS  AND  ETIOLOGY  61 

sels ;  in  infants  we  have  seen  this  occasioned  by  pressure 
exerted  on  the  lower  end  of  the  thigh  to  ascertain  the 
presence  of  tenderness.  Viewing  the  situation  broadly, 
it  must  be  acknowledged  that  except  for  the  realization 
that  scurvy  is  due  to  a  new  food  factor — a  vitamine — our 
fundamental  understanding  of  its  pathogenesis  has  ad- 
vanced but  little,  in  spite  of  the  employment  of  experi- 
mental methods  and  the  availability  of  modern  technic. 

It  is  doubtful  whether  mere  clinical  studies  will  con- 
tribute in  a  large  measure  to  the  solution  of  the  patho- 
genesis of  scurvy.  Much  may,  however,  be  learned  by 
investigations  of  the  metabolism  in  human  scurvy — an 
aspect  of  the  problem  which,  as  will  be  brought  out  in  a 
subsequent  chapter,  hardly  has  been  explored.  By  this 
means  may  be  acquired  a  clearer  understanding  of  the 
effect  of  an  antiscorbutic  deficiency  on  the  tissues  and  on 
cellular  activity.  Much  may  be  expected  from  physiologic 
and  pharmacologic  studies  of  the  specific  vitamine,  al- 
though it  is  not  yet  available  in  a  pure  state.  Finally,  it  is 
probable  that  the  solution  of  similar  questions  relating 
to  the  pathogenesis  of  cognate  disorders — a  study  which 
is  engaging  the  best  efforts  of  so  many  workers  through- 
out the  world — will  shed  light  on  this  particular  disease. 


CHAPTER  III 
THE  ANTISCORBUTIC  VITAMINE  1 

We  shall  not  discuss  the  subject  of  vitamines  in  gen- 
eral, but  confine  ourselves  to  the  more  limited  field  of  the 
antiscorbutic  vitamine.  The  recognition  of  the  "  acces- 
sory" dietary  factors  is  of  such  recent  date,  however,  that 
it  will  be  well  to  consider  briefly  how  attention  came  to 
be  directed  to  them  and  how  their  existence  was  ascer- 
tained. As  in  the  case  of  so  many  scientific  discoveries, 
it  is  difficult  to  point  to  the  exact  time  when  the  advance 
was  made.  On  looking  back  we  find  that  Lunin,  in  1881, 
noting  that  mice  were  unable  to  live  on  a  diet  consisting 
of  protein,  fats,  carbohydrates,  salts  and  water,  came  to 
the  conclusion  "that  other  substances  indispensable  to 
nutrition  must  be  present  in  milk  besides  caseinogen,  fat, 
lactose  and  salts.' '  This  work  did  not  stimulate  similar 
investigations,  nor  did  Lunin,  as  might  have  been  ex- 
pected, allude  to  scurvy.  The  work  which  f  ocussed  atten- 
tion on  this  novel  aspect  of  dietetics  was  the  report  of 
Eijkmann,  in  1897,  to  the  effect  that  when  fowl  are  fed 
decorticated  rice,  they  develop  a  disease  resembling  beri- 
beri, and  that  the  paralytic  symptoms  disappear  on  feed- 
ing them  rice  polishings  or  its  alcoholic  extract.  Here, 
for  the  first  time,  was  a  positive  rather  than  a  negative 
experiment,  and  one  capable  of  simple  verification.  The 
subject  was  placed  on  a  scientific  basis  by  the  classic  in- 
vestigation of  Hopkins,  who  experimented  with  purified 

1  Vitamine  is  used  throughout  this  monograph  as  synonymous  with  "ac- 
cessory food  factor"  or  "food  hormone"  as  a  convenient  descriptive  term, 
without  any  intention  of  connoting  a  definite  chemical  substance. 

62 


THE  ANTISCORBUTIC  VITAMINE  63 

food  substances,  and  demonstrated  how  diets  which  were 
deficient  could  be  rendered  adequate.  As  early  as  1906 
he  wrote  "the  animal  body  is  adjusted  to  live  either  upon 
plant  tissues  or  other  animals,  and  these  contain  countless 
substances  other  than  the  proteins,  carbohydrates  and 
fats."  "In  diseases  such  as  rickets,  and  particularly  in 
scurvy,  we  have  had  for  long  years  knowledge  of  a  dietetic 
factor,  but  though  we  know  how  to  benefit  these  conditions 
empirically,  the  real  errors  in  the  diet  are  to  this  day  quite 
obscure. "  The  work  of  Osborne  and  Mendel,  and  Mc- 
Collum  and  Davis  in  this  country,  of  Schaumann,  Funk, 
Stepp  and  others,  all  led  to  the  conclusion  that  purified 
diets  are  unable  to  satisfy  the  nutritive  requirements  of 
rats  or  mice,  and  that  extracts  of  the  natural  foods  suffice 
to  render  the  diet  adequate. 

The  same  rule  holds  for  man,  who,  when  deprived  of 
these  vitamines,  develops  the  so-called  deficiency  diseases 
— typically  modem  disorders.  Eegarded  as  a  group,  they 
are  a  consequence  of  our  altered  mode  of  life  and  peculiar 
civilization.  They  follow  naturally  upon  the  development 
of  immense  cities  housing  millions  of  people,  who  neces- 
sarily must  receive  perishable  foodstuffs  produced  at  a 
great  distance.  To  even  a  greater  extent  they  are  the 
product  of  countless  ingenious  methods  devised  mainly  to 
render  foods  stable — drying,  heating,  the  addition  of  pre- 
servatives— most  of  which  accomplish  their  object,  but 
incidentally  rob  the  food  of  its  essential  vitamine. 

None  of  the  vitamines  has  been  isolated  in  a  pure  state. 
The  nearest  approach  to  this  desired  end  has  been  the 
work  of  Funk,  who  obtained  the  water-soluble  vitamine 
in  a  state  of  such  concentration  that  about  3  mg.  sufficed 
to  cure  a  pigeon  of  polyneuritis.  In  considering  the 
attributes  of  the  antiscorbutic  vitamine,  it  must  be  borne 


64  SCURVY:    PAST  AND  PRESENT 

in  mind  that  this  factor  is  referred  to  as  it  exists  in 
various  foods ;  for  example,  in  orange  juice  or  in  cabbage, 
and  furthermore,  that  the  method  of  ascertaining  its 
presence  or  concentration  is  limited  to  the  crude  biological 
test  of  animal  feeding. 

The  antiscorbutic  factor  is  distinguished  by  being  the 
most  sensitive  of  the  three  vitamines,  the  most  unstable, 
the  least  resistant  to  physical  or  chemical  processes.  It 
may  be  regarded  as  one  of  the  most  delicate  indicators  of 
the  biological  integrity  of  foodstuffs;  however,  as  Falk 
and  his  co-workers  have  shown,  the  enzyme  property  of 
living  matter  is  still  more  readily  destroyed.  The  anti- 
scorbutic vitamine  is  soluble  in  water,  and  therefore  is 
termed  by  some  the  "water-soluble  C"  factor.  It  is  also 
soluble  in  alcohol,  as  shown  by  the  experiments  of  Hess 
and  Unger  and  of  Harden  and  Zilva,  and  the  therapeutic 
tests  on  infants  of  Freise  and  of  Freudenberg.2  It 
possesses,  therefore,  the  solubility  of  the  water-soluble 
vitamine.  Some  have  suggested  that  it  may  be  derived 
from  this  vitamine,  others  that  instead  of  one  there  may 
be  a  series  of  antiscorbutic  factors — suggestions  based  on 
pure  hypothesis.  Hoist  and  Froelich  showed  that  this 
vitamine  passes,  without  appreciable  loss,  through  dialyz- 
ing  parchment,  and  Harden  and  Zilva  (2)  that  it  can  pass 
through  a  porcelain  filter.  The  latter,  using  the  method 
of  Seidell,  demonstrated  that  this  vitamine  is  not  ad- 
sorbed by  fine  precipitates  such  as  fuller's  earth,  differ- 
ing in  this  respect  from  the  water-soluble  vitamine ;  and 
that  in  a  mixture  of  equal  volumes  of  autolyzed  yeast  and 

2  Freise  cured  a  case  of  infantile  scurvy  by  giving  about  2  c.c.  of  an 
extract  obtained  from  turnips  by  means  of  absolute  alcohol.  Seven  weeks 
were  necessary  to  cause  a  disappearance  of  symptoms.  Freudenberg  employed 
an  extract  of  carrots,  prepared  with  96  per  cent,  alcohol,  and  effected  a 
quicker  cure. 


THE  ANTISCORBUTIC  VITAMINE  65 

orange  juice,  the  antiscorbutic  vitamine  remained 
unaffected,  whereas  the  water-soluble  A  was  en- 
tirely removed. 

One  of  the  most  distinctive  characteristics  of  the  anti- 
scorbutic factor  is  its  sensitiveness  to  even  moderately 
high  degrees  of  heat.  In  this  respect  it  differs  markedly 
from  the  water-soluble  or  so-called  ' '  antineuritic  vita- 
mine"  which  withstands  exposure  to  high  temperature. 
The  reaction  of  the  antiscorbutic  vitamine  in  this  regard 
is  not  a  simple  one,  and  cannot  be  expressed  by  a  mere 
statement  of  the  degree  of  heat  and  the  length  of  ex- 
posure. Numerous  other  factors,  especially  the  reaction 
of  the  medium,  but  also  the  physical  environment,  must 
be  taken  into  consideration — for  example,  cabbage  is  more 
resistant  to  the  action  of  heat  than  its  juice.  An  under- 
standing of  the  relation  of  antiscorbutics  to  heat  may  per- 
haps best  be  obtained  by  considering  the  subject  in  con- 
nection with  some  definite  foodstuffs.  The  most  exhaust- 
ive study  from  a  quantitative  standpoint  is  that  of  Delf . 
She  showed  that  when  cabbage  is  subjected  for  an  hour 
to  a  temperature  of  80°  to  100°  C,  90  per  cent,  of  its 
antiscorbutic  vitamine  is  lost,  and  that  80  per  cent,  is 
lost  when  a  temperature  of  90°  to  100°  is  maintained  for 
twenty  minutes,  or  a  temperature  of  60°  for  a  period  of 
sixty  minutes.  This  experiment  shows  that  the  destruc- 
tive influence  of  heat  is  enhanced  to  a  comparatively 
slight  degree  by  a  rise  of  temperature,  only  about  three- 
fold when  it  is  raised  from  60°  C.  to  the  boiling-point. 
This  result  points  to  a  temperature  coefficient  of  about 
1.5  to  10°  C.  of  temperature.  It  is  suggested  by  Delf 
that  this  low  coefficient  of  destruction  is  opposed  to  the 
enzyme  or  protein-like  theory  of  the  nature  of  the  vita- 
mine, and  suggests  a  simpler  constitution.    On  the  other 

5 


66  SCURVY:    PAST  AND  PRESENT 

hand,  we  must  bear  in  mind  that  the  proteins  which  have 
been  used  in  experiments  and  found  to  possess  a  high 
coefficient  of  heat,  have  been  tested  in  the  pure  state, 
whereas  the  vitamine  of  the  cabbage  is  bound  up  in  the  cell. 

Experiments  with  this  vitamine  as  , found  in  milk 
accord  with  the  above  investigation,  demonstrating  that 
intensity  of  heat  is  not  as  destructive  as  prolonged  heating. 
This  agrees  with  the  clinical  experience  that  milk  which 
has  been  boiled  for  a  few  minutes  does  not  induce  scurvy 
as  readily  as  pasteurized  milk  which  has  been  heated  for 
45  minutes  to  140°  or  165°  F.  (Hess  and  Fish). 

As  demonstrated  by  tests  with  orange  and  with  lemon 
juice,  the  antiscorbutic  vitamine  is  greatly  protected  from 
the  destructive  effect  of  heat  when  it  is  associated  with 
an  acid.  This  was  shown  first  by  Hoist  and  Froelich  and 
has  been  confirmed  by  numerous  observers.  An  excellent 
example  of  marked  thermostability  conferred  on  a  food 
by  its  acid  reaction  is  furnished  by  the  tomato,  which  is 
strongly  antiscorbutic  even  after  it  has  been  subjected  to 
the  canning  process.  Conversely,  Harden  and  Zilva  have 
shown  that  the  vitamine  is  destroyed  by  alkali  even  when 
dilute  (one-fiftieth  normal  sodium  hydrate)  and  kept  in 
contact  at  room  temperature ;  this  alteration  does  not  take 
place  at  once,  but  in  the  course  of  several  hours. 

It  is  true  that  the  antiscorbutic  factor  is  peculiarly 
sensitive  to  drying,  but  there  are  exceptions  to  this  rule, 
so  that  it  is  incorrect  to  state,  as  does  the  British  Report 
of  the  Medical  Research  Committee,  that  "it  may  be 
regarded  as  an  axiom  that  dry  or  dried  foodstuffs  will 
not  prevent  scurvy."  We  have  shown  that  fresh  milk 
dried  by  the  Just-Hatmaker  process  may  retain  by  far 
the  greater  moiety  of  its  virtue.  In  this  regard  rapidity 
of  desiccation  and  subsequent  protection  from  oxidative 


THE  ANTISCORBUTIC  VITAMINE  67 

processes  are  important  factors.  The  general  rule  holds 
true,  however,  that  this  vitamine,  in  contradistinction  to 
the  "water-soluble"  vitamine,  is  readily  damaged  and 
destroyed  by  drying. 

This  vitamine  is  peculiarly  sensitive  to  aging,  espe- 
cially when  it  is  present  in  an  alkaline  or  neutral  medium ; 
but  even  in  an  acid  medium  its  potency  soon  diminishes. 
Harden  and  Zilva  found  this  to  be  the  case  with  lemon 
juice  stored  for  a  fortnight  in  the  cold  room,  and  our 
experience  has  been  similar  in  regard  to  orange  juice  kept 
in  the  refrigerator  under  a  layer  of  liquid  petrolatum. 
In  milk  the  antiscorbutic  factor  diminishes  with  age,  espe- 
cially following  pasteurization,  in  the  course  of  which 
most  of  the  acid-forming  bacteria  have  been  destroyed. 
Aging  has  the  least  effect  when  the  food  with  which  the 
vitamine  is  associated  has  been  dried.  This  is  true  not 
only  of  lemon  and  of  orange  juice  as  demonstrated  experi- 
mentally and  clinically,  but  even  of  milk,  which  even  after 
it  has  been  dried  and  stored  for  months,  may  still  possess 
marked  curative  value.3 

Experiments  by  Harden  and  Zilva  showed  that  ex- 
posure of  lemon  juice  to  ultra-violet  rays  for  eight  hours 
does  not  influence  its  antiscorbutic  activity,  that  exposure 
of  autolyzed  yeast  for  the  same  length  of  time  likewise 
does  not  impair  its  "  antineuritic ' '  potency,  but  that  under 
identical  conditions  the  fat-soluble  factor  in  butter  be- 
comes inactivated.  Similar  tests  carried  out  by  the  author 
with  orange  juice  led  to  the  same  result.  It  thus  appears 
that  one  of  the  vitamines — not  the  most  unstable — mani- 
fests a  peculiar  sensitiveness  to  a  certain  form  of  physical 
or  chemical  action. 

8  Reference  is  made  to  a  milk  dried  by  the  .Tust-Hatmaker  process,  con- 
taining about  3  per  cent,  of  moisture.  The  clinical  data  on  -which  this  con- 
clusion is  based  are  given  in  the  previous  chapter. 


68  SCURVY:    PAST  AND  PRESENT 

In  view  of  the  fact  that  shaking  partly  destroys  pepsin 
and  rennin,  as  shown  by  Shaklee  and  Meltzer,  it  would  be 
of  interest  to  ascertain  whether  this  process  brings  about 
any  impairment  of  the  antiscorbutic  vitamine.  Particu- 
lar interest  is  attached  to  this  question  because  it  is 
generally  recognized  that  milk  loses  some. of  its  potency 
in  the  course  of  handling — whatever  may  be  comprised  by 
this  term.  In  experiments  on  the  fat-soluble  vitamine 
Steenbock  and  his  co-workers  found  that  "somewhere  in 
the  course  of  the  manipulation  to  which  the  butter  fat  had 
been  subjected,  factors  had  been  introduced  which  were 
responsible  for  a  vitamine  destruction. ' ' 

Before  discussing  the  question  of  the  manner  in  which 
the  antiscorbutic  vitamine  functionates,  it  may  be  well  to 
state  briefly  the  type  of  the  disturbance  which  its  defi- 
ciency occasions.  The  chief  manifestation  is  damage  to 
the  integrity  of  the  endothelium  of  the  vessels,  resulting  in 
hemorrhage — whether  from  diapedesis  or  from  rhexis 
or  both  of  these  conditions,  the  microscope  does  not  in- 
form us.  Nor  can  it  be  stated  positively  that  the  endothe- 
lium has  not  been  injured  by  a  secondary  toxic  or  bacterial 
factor.  However  this  may  be,  the  end  result  of  the  defi- 
ciency is  endothelial  damage,  a  pathologic  condition  which 
may  be  demonstrated  clinically  in  scurvy  by  the  "capil- 
lary resistance  test"  (chapter  VII).  The  other  marked 
functional  alteration  in  scurvy  is  increased  susceptibility 
to  infection;  but  how  a  vitamine  deficiency  induces  this 
vulnerability  cannot  be  explained.  Clinical  tests  show 
that  the  blood  contains  sufficient  antitoxin  (diphtheria)  to 
afford  protection.  Harden  and  Zilva  found  that  "guinea- 
pigs  fed  on  an  unrestricted  mixed  diet,  on  a  quantitatively 
restricted  mixed  diet,  and  a  scorbutic  diet  showed  no  dif- 
ferentiation in  amboceptor  and  agglutinin  titres,  and  in 


THE  ANTISCORBUTIC  VITAMINE  69 

the  complement  activity  of  the  blood."  If  this  is  to  be 
interpreted  as  indicating  that  the  protective  substances  of 
the  body  undergo  but  little  alteration,  we  must  consider 
whether  susceptibility  to  infection,  as  well  as  tendency  to 
hemorrhage,  is  not  due  largely  to  alteration  in  the  cement 
substance  of  the  endothelial  and  epithelial  membranes. 

The  Mode  of  Action  of  the  Vitamine. — One  of  the  most 
interesting  as  well  as  puzzling  questions  in  regard  to  the 
antiscorbutic  vitamine  concerns  the  manner  in  which  it 
prevents  or  cures  scurvy.  It  is  a  subject  which  at  present 
is  in  a  state  of  flux,  hardly  having  emerged  from  the  realm 
of  hypothesis,  so  that  detailed  consideration  will  profit 
little.  At  first  the  modus  operandi  was  explained  and 
accepted  as  enzyme  action,  but  it  was  soon  evident,  in 
view  of  the  thermostability  of  the  vitamine,  that  it  could 
not  be  classed  as  a  ferment  or  enzyme  in  the  generally- 
accepted  sense  of  this  term.  In  general,  it  may  be  stated 
that  there  are  two  main  views :  one  that  the  vitamine  acts 
directly,  and  the  other  that  it  acts  indirectly  through  the 
function  of  the  endocrine  glands.  Direct  action,  further- 
more, may  be  accomplished  in  at  least  one  of  three  ways. 
The  vitamine  may  (1)  serve  as  a  source  of  nutriment  for 
the  tissues,  (2)  exert  an  antitoxic  effect  on  toxic  products, 
or  (3)  function  as  a  catalyzer.  The  first  interpretation  is 
evidently  the  simplest  and  conforms  to  the  long-estab- 
lished knowledge  of  caloric  food  factors.  That  such  small 
amounts  as  2  c.c.  of  orange  juice  daily  should  suffice  to 
protect  an  animal  from  nutritional  disaster  runs  counter, 
however,  to  former  conceptions  of  food  nutrition.  Fur- 
ther than  this  there  is  little  against  this  viewpoint.  In  its 
favor  is  the  fact  that,  up  to  a  certain  point,  antiscorbutics 
act  in  direct  ratio  to  the  amount  given ;  for  example,  2  c.c. 
of  canned  tomato  juice  is  insufficient  to  prevent  scurvy  in 


70  SCURVY:    PAST  AND  PRESENT 

guinea-pigs,  3  c.c.  will  protect  some  but  not  all  of  a  series, 
whereas  when  the  amount  is  increased  to  4  c.c.  daily  all 
animals  will  be  saved.  As  we  are  considering  new  food 
factors  it  is  manifestly  unwise  to  judge  them  by  old  stand- 
ards, and  to  decide  offhand  that  they  cannot  possess  such 
a  high  degree  of  nutritive  power.  This  question  must  be 
regarded  as  still  open. 

The  antitoxic  theory  suffers  from  the  fact  that  the 
toxic  origin  of  scurvy  cannot  be  established.  Before  this 
is  possible,  it  is  clear  that  it  will  be  difficult  to  bring  for- 
ward convincing  evidence  of  a  neutralizing  substance. 
Against  this  theory  is  the  fact  that  elimination  therapy  is 
of  no  avail  in  the  treatment  of  infantile  scurvy.  Hess  and 
Unger  (1919)  failed  to  alleviate  the  symptoms  by  means 
of  catharsis,  diuresis,  sweating  and  repeated  intravenous 
injections  of  normal  salt  solution.  In  its  favor  it  may  be 
advanced,  in  a  general  way,  that  the  vitamine,  in  many 
characteristics,  resembles  an  antitoxin — in  its  extreme 
lability,  its  destruction  by  heat,  aging  and  alkalies.  On 
the  other  hand,  antitoxins  also  are  readily  destroyed  by 
acid  which,  as  has  been  shown,  exerts  a  protective  influence 
on  the  antiscorbutic  factor.  The  rapidity  of  action  of  the 
vitamines,  one  of  the  most  impressive  phenomena,  calls 
to  mind  the  neutralizing  action  of  an  antitoxin,  and  prob- 
ably has  given  rise  to  the  analogy.  Williams  suggests 
that  the  vitamines  have  "a  general,  non-specific,  antitoxic 
or  eliminative  action' '  on  toxic  substances  resulting  from 
the  metabolic  decomposition  of  food. 

The  theory  has  been  advanced  that  the  action  of  the 
vitamines  is  catalytic.  Although  this  viewpoint  has  been 
taken  regarding  the  water-soluble  rather  than  the 
antiscorbutic  vitamine,  it  will  be  well  to  review  briefly 
the  work  on  which  it  is  based.    Among  the  first  to  suggest 


/ 


THE  ANTISCORBUTIC  VITAMINE  71 

this  hypothesis  were  Vedder  and  Clark,  who  noted  a  rela- 
tionship between  the  amount  of  vitamine  required  by  fowls 
and  their  carbohydrate  intake.  Funk  in  1913  made  a  simi- 
lar observation  in  regard  to  beriberi,  and  in  the  f  ollowing 
year,  with  von  Schoenborn,  showed  that  a  vitamine-free 
diet  led  to  hyperglycemia,  with  diminished  amount  of 
hepatic  glycogen,  and  that  the  addition  of  water-soluble 
vitamine  diminished  the  hyperglycemia  and  increased  the 
liver  glycogen.  The  work  of  Burge  and  his  co-workers  on 
the  catalase  content  of  tissue  led  to  a  similar  conclusion. 
Their  results  may  be  summarized  by  the  statement  that 
the  oxidative  processes  are  hampered  and  fail  to  balance 
the  autolytic  changes,  and,  furthermore,  that  a  relation- 
ship exists  between  the  catalase  activity,  acidosis  and 
normal  oxidative  processes.  This  theory  would  presup- 
pose that  scurvy  is  due  to  the  formation  of  toxins 
which  are  normally  in  process  of  continual  destruction 
in  the  body.  According  to  some,  these  catalyzed 
toxic  substances  are  metabolic  in  character,  originating 
from  incompletely  oxidized  food;  according  to  another 
interpretation,  they  are  the  product  of  autolyzed  tissue 
cells  (tissue  toxins).  The  difficulty  with  this  explanation 
is  that  scurvy  cannot  be  prevented  or  cured  by  a  diet  con- 
taining food  of  high  catalytic  power.  For  example,  wheat 
embryos  which,  according  to  recent  investigations  of 
Crocker  and  Harrington,  have  a  high  catalytic  activity, 
were  found  of  no  therapeutic  value  in  relation  to  infantile 
scurvy  (Hess,  3). 

This  problem  has  been  approached  from  quite  a  dif- 
ferent angle.  As  is  well  known,  certain  bacteria  require 
serum,  blood,  milk,  etc.,  in  order  to  grow  satisfac- 
torily on  artificial  culture  media.  It  has  been  estab- 
lished recently,  primarily  by  the  work  of  Lloyd,  that 


72  SCURVY:    PAST  AND  PRESENT 

this  peculiarity  in  the  cultivation  of  microorganisms  is 
due  largely  to  their  requirement  of  vitamine.  She  found 
a  relationship  of  the  inverse  order  between  the  amount  of 
amino  acid  present  in  the  culture  medium  and  the  amount 
of  vitamine  required  to  stimulate  the  growth  of  strains  of 
meningococcus.  Reasoning  from  this  experience,  she  sug- 
gests that  the  action  of  the  accessory  growth  factors  is  to 
increase  the  reaction  velocity  of  the  proteolytic  metabo- 
lism. Here  we  find  the  vitamines  once  more  regarded  as 
catalyzers.  This  author,  however,  associates  their  activity 
with  proteolytic  rather  than  with  carbohydrate  metabo- 
lism. Interesting  and  suggestive  work  of  similar  nature 
has  been  carried  out  in  relation  to  the  growth  of  protozoa 
and  of  yeasts  (Eddy) .  Investigations  of  this  kind,  dealing 
with  unicellular  organisms  propagated  on  a  simple  food, 
have  the  advantage  of  greatly  simplifying  the  problem. 

The  recent  work  of  Dutcher  falls  under  this  caption, 
differing  merely  in  the  fact  that  he  attributes  to  the  vita- 
mines  an  indirect  action.  He  has  demonstrated  that  the 
tissues  of  polyneuritic  birds  show  a  decrease  in  catalase 
activity  to  a  point  56  per  cent,  below  normal,  and  that 
this  activity  is  largely  restored  when  the  birds  are  cured 
with  vitamine.  According  to  this  writer  the  vitamine 
functions  as  a  metabolic  stimulant,  and  its  lack  results 
in  a  depression  of  the  body  oxidations  with  an  accompany- 
ing formation  of  toxic  metabolic  products,  injurious  to  the 
nervous  system.  The  action  is  regarded  as  coming  about 
in  an  indirect  manner,  being  accomplished  through  the 
hormone  action  of  the  vitamines  on  one  or  more  glands  of 
internal  secretion. 

The  endocrine  hypothesis,  suggested  by  Funk  in  his 
monograph,  is  not  without  some  corroborative  evidence. 
In  testing  the  pharmacologic  action  of  the  water-soluble 


THE  ANTISCORBUTIC  VITAMINE  73 

vitamine,  Uhlmann  found  that  it  stimulated  the  various 
glands  of  the  digestive  tract,  in  this  respect  acting  like 
pilocarpine.  Some  years  ago  Albert  expressed  the  opin- 
ion that  the  action  of  this  vitamine  was  ' 'vagotropic' '  like 
atropine,  and  recently  Dutcher  has  reported  definite  relief 
and  cessation  of  polyneuritic  symptoms  by  means  of  pilo- 
carpine (0.5  mg.  subcutaneously).  He  claims  equally 
good  results  from  thyroxin,  the  hormone  of  the  thyroid 
gland,  from  desiccated  thyroid  and  from  tethelin  (pitui- 
tary). Voegtlin  and  Myers  conclude,  as  the  result  of 
experiments  with  brewers'  yeast,  that  the  chemical  and 
physical  properties  of  secretine  and  vitamine  are  identical. 
The  early  work  of  Funk  and  Douglas,  which  showed 
that  various  glands  of  internal  secretion  diminish  in  size 
and  undergo  degenerative  changes  when  the  diet  is  vita- 
mine-free,  the  newer  work  of  McCarrison  and  of  Dutcher 
to  the  same  effect,  clearly  point  to  an  intimate  relationship 
between  some  of  the  endocrine  glands  and  the  vitamines. 
As  regards  scurvy,  the  only  work  is  that  of  Eondoni, 
McCarrison  and  of  La  Mer  and  Campbell  on  the  adrenal 
glands,  which  were  found  by  all  to  be  enlarged  in  guinea- 
pigs  suffering  from  this  disorder.  These  investigations 
must  be  regarded  as  tentative  rather  than  conclusive  until 
confirmed  by  similar  necropsy  reports  in  man.  In  this 
connection  it  should  be  noted  that  thyroid,  parathyroid  or 
suprarenal  extract  is  of  no  avail  in  the  treatment  of  scurvy. 
This  failure  may,  however,  be  explained  by  the  fact  that 
the  normal  balance  of  glandular  activity  was  not  estab- 
lished. We  must  bear  in  mind,  however,  that  although  the 
vitamines  may  influence  the  secretion  of  the  glands  of  in- 
ternal secretion,  this  explanation  does  not  satisfactorily 
account  for  the  symptoms  of  the  " deficiency  diseases." 
These  disorders  do  not  in  the  slightest  respect  resemble 


74  SCURVY:    PAST  AND  PRESENT 

the  clinical  pictures  which  we  are  accustomed  to  associate 
with  a  lack  of  activity  of  the  glands  of  internal  secretion. 
If  the  polyneuritis  of  beriberi  and  the  hemorrhages  of 
scurvy  are  attributable  to  a  diminished  secretion  of  the 
endocrine  glands,  then  it  will  be  necessary  to  revise  pres- 
ent conceptions  of  their  physiologic  functions. 

The  Fate  of  the  Vitamine  in  the  Body. — One  of  the  most 
important  questions  in  relation  to  the  antiscorbutic  vita- 
mine,  quite  apart  from  its  chemical  nature,  physiologic 
function,  and  its  source,  is  its  fate  in  the  human  body 
after  it  has  reached  the  alimentary  canal  or  been  carried 
to  the  tissues.  It  can  be  readily  appreciated  that  our 
knowledge  of  this  aspect  is  very  meagre.  We  shall  en- 
deavor, however,  to  detail  what  little  is  known  of  this 
subject,  conscious  of  the  fact  that  investigations  of  the 
next  few  years  may  contradict  our  present  viewpoints. 

Most  of  the  constituents  necessary  for  the  construction 
of  tissue  or  for  carrying  on  its  functions  can  be  synthe- 
sized by  the  animal  body  from  the  basal  foodstuffs.  It 
has  been  ascertained  within  the  past  decade  that  certain 
constituents — for  example,  some  amino-acids  of  the  pro- 
tein molecule — are  building-stones  which  cannot  be  pri- 
marily elaborated  by  the  cells,  but  must  be  supplied  by  the 
food.  At  present  the  vitamines — including  the  antiscorbu- 
tic vitamine — are  included  in  this  new  and  essential  group 
of  substances  which  the  human  organism  cannot  manufac- 
ture. Animal  experiments  seem  to  bear  out  this  concep- 
tion of  the  vitamine  whether  we  regard  them  as  dynamic 
or  as  indispensable  tissue  elements  in  the  structural  sense. 

A  closely-related  but  less  fundamental  question  is  that 
of  the  ability  of  man  to  store  vitamines — whether  the  tis- 
sues can  hoard  an  excess  of  these  factors,  or  whether,  in 
this  respect,  we  are  carrying  on  a  precarious  hand-to- 


THE  ANTISCORBUTIC  VITAMINE  75 

mouth  existence  in  regard  to  cellular  nutrition.  It  is  of 
course  clear  that  at  all  times  the  various  organs  and 
tissues  must  contain  a  certain  amount  of  the  vitamines. 
This  has  been  shown  for  the  water-soluble  or  "antineu- 
ritic  vitamine ' '  by  the  fact  that  even  the  organs  of  birds 
which  have  died  of  polyneuritis  contain  an  appreciable 
quantity  of  the  specific  vitamine,  although  an  insufficiency 
of  this  very  factor  has  led  to  their  death.  That  such 
is  the  case  is  demonstrated  for  the  antiscorbutic  vitamine 
by  the  fact  that  muscle  tissue  contains  sufficient  anti- 
scorbutic to  protect  individuals  subsisting  largely  on  a 
diet  of  which  raw  meat  constitutes  the  sole  antiscorbutic 
agent  (Stefansson).  It  is  very  probable  that  some  organs 
contain  more  of  the  vitamines  than  others ;  this  has  been 
proved  for  the  i '  antineuritic ' '  factor,  and  seems  to  hold 
good  for  the  antiscorbutic — the  liver  being  particularly 
rich.    No  quantitative  study  has  been  carried  out  from 


this  point  of  view  regarding  the  antiscorbutic  vitamine, 
and  it  would  be  well  worth  our  while  to  ascertain  the  rela- 
tive antiscorbutic  potency  of  the  various  organs  of  the 
body.  Some  time  ago  we  undertook  experiments  to  deter- 
mine whether  the  guinea-pig  is  capable  of  storing  this 
vitamine.  One  series  of  guinea-pigs  was  fed  daily  6  c.c. 
of  orange  juice  for  a  period  of  two  weeks,  whereas  another 
series,  of  about  the  same  weight,  was  given,  in  addition  to 
the  basal  ration,  only  3  c.c.  per  capita  (the  minimal  pro- 
tective dose).  After  this  preliminary  period  both  series 
were  placed  on  a  diet  containing  practically  no  antiscor- 
butic. Both  groups  came  down  with  scurvy  after  about 
the  same  interval,  leading  to  the  conclusion  that  there 
could  have  been  little  if  any  storing  of  the  excess  vitamine 
by  those  which  received  twice  the  "minimal  protective 
dose."    The  experiments  of  Harden  and  Zilva,  who  fed  a 


76  SCURVY:    PAST  AND  PRESENT 

concentrated  lemon  juice,  showed  that  this  potent  agent 
also  was  unable  to  provide  against  a  subsequent  period  of 
antiscorbutic  deficiency.  It  should  be  realized  that  the 
results  of  these  tests  on  guinea-pigs  cannot  be  applied  to 
man  without  tests  on  other  species. 

It  might  be  thought  that  the  blood — the  purveyor  of 
the  vitamines  to  the  tissues — would  be  particularly  rich 
in  these  essential  factors.  Such,  however,  w^as  not  our 
experience  in  respect  to  the  antiscorbutic  vitamine.  The 
blood  possibly  varies  greatly  in  this  respect  according  to 
the  diet  of  the  individual,  or  even  according  to  the  inter- 
val elapsing  after  the  ingestion  of  antiscorbutic  food. 
Our  opinion  is  based  on  the  surprisingly  poor  therapeutic 
effect  of  blood  transfusion  in  the  treatment  of  scurvy. 
To  illustrate:  An  infant  weighing  about  fifteen  pounds 
received  six  intravenous  injections  of  citrated  blood — 
one  of  200  c.c,  given  by  the  direct  method,  and  a  month 
later  five  smaller  transfusions  with  citrated  blood,  which 
aggregated  205  c.c.4  In  spite  of  this  addition  of  blood, 
the  hemorrhage  and  congestion  of  the  gums  did  not  dis- 
appear, nor  the  general  condition  improve,  as  would  have 
happened  had  50  or  75  c.c.  of  orange  juice  been  given  by 
mouth.  It  seems  probable  that  small  quantities  of  vita- 
mine  are  being  transmitted  at  all  times  by  the  blood  and 
supplied  to  the  cells,  but  that  its  normal  content  of  this 
factor  is  not  great.  The  antiscorbutic  potency  of  blood 
may  perhaps  be  compared  to  that  of  milk.  Animal  in- 
vestigation may  show  that  various  vessels — for  example, 
those  supplying  or  draining  certain  glandular  organs — 
differ  in  the  antiscorbutic  quality  of  the  blood  which  they 

*  The  dates  and  quantities  of  the  transfusions  were  as  follows:  March 
26th,  200  c.c.;  April  27th,  30  c.c.;  April  28th,  35  c.c;  April  29th,  30  c.c; 
May  2nd,  75  c.c ;  May  3rd,  35  c.c 


THE  ANTISCORBUTIC  VITAMINE  77 

carry.  It  is  evident,  therefore,  that  many  transitory 
factors  may  influence  the  vitamine  content  of  the  blood, 
and  that — as  in  the  case  of  milk  and  frnits  and  vege- 
tables— we  are  not  dealing  with  a  constant  and  un- 
varying agent. 

Nothing  whatsoever  is  known  concerning  the  excretion 
of  the  antiscorbutic  vitamine.  No  attempts  have  been 
made  to  recover  it  from  the  urine,  or  to  ascertain  if,  when 
large  amounts  are  ingested,  the  excess  is  thrown  off  by  the 
body.  This  suggests  the  question — a  corollary  of  that 
raised  in  connection  with  the  vitamine  content  of  the 
blood — whether  it  is  immaterial  if  the  vitamine  is  taken 
frequently  in  small  amounts,  or  is  provided  only  occa- 
sionally and  at  longer  intervals  in  larger  amounts.  Is  it 
of  no  moment  whether  the  infant  receive  its  quota  of 
antiscorbutic  every  few  hours  through  the  medium  of  the 
breast  milk,  or  only  once  a  day  in  the  form  of  orange 
juice  or  tomato  1  If  we  turn  to  studies  on  the  other  vita- 
mines  for  enlightenment  as  to  the  possibility  of  excretion, 
we  find  that  Muckenfuss  recovered  the  water-soluble  fac- 
tor from  ox  bile  and  from  human  urine.5  In  this  article 
he  proposes  the  interesting  question  of  a  possible  varia- 
tion in  the  vitamine  output  under  pathological  conditions, 
which  may  be  responsible  for  the  development  of  func- 
tional disturbances  in  children. 

It  would  be  of  interest  to  know  the  fate  of  the  antiscor- 
butic vitamine  in  the  g astro-intestinal  tract.  How  is  it 
affected  by  a  lack  of  the  acid  gastric  juice,  or 
by  the  alkaline  intestinal  secretions,  or  by  the  bac- 
teria in  the  lumen  of  the  gut?    From  which  part  of  the 

5  This  investigation  was  carried  out  by  means  of  activating  fuller's 
earth  with  these  fluids.  This  method  is  inapplicable  to  the  antiscorbutic  vita- 
mine, which  is  not  adsorbed  by  this  material.  An  attempt  to  feed  concen- 
trated human  urine  to  guinea-pigs  resulted  in  their  death. 


78  SCURVY:    PAST  AND  PRESENT 

intestine  is  it  largely  absorbed?  May  an  appreciable 
amount  undergo  destruction  before  this  is  accomplished? 
None  of  these  questions  can  be  answered  satisfactorily  in 
the  present  state  of  our  knowledge,  but  they  suggest  that 
the  mere  fact  that  an  adequate  quota  of  antiscorbutic  vita- 
mine  is  provided  in  the  food  does  not  necessarily  insure  an 
adequate  supply  for  the  tissues.  If  in  addition  to  the 
question  of  intake  we  must  take  into  account  that  the  vita- 
mines  may  suffer  various  vicissitudes,  it  may  come  to  pass 
that  pathological  conditions  at  times  destroy  or  render 
them  partially  inactive.  In  this  way  we  may  account  for 
irregularities  in  the  clinical  course  of  disorders  associated 
with  vitamine  deficiency. 

Of  prime  importance,  however,  is  the  effect  of  the 
vitamines  on  the  glands  of  the  alimentary  tract  and  on 
the  digestive  processes.  A  diminution  of  gastric  juice,  or 
in  some  instances  a  total  absence,  has  been  observed  in 
adult  scurvy,  and  noted  by  us  in  two  cases  of  infantile 
scurvy.  As  mentioned  elsewhere,  some  consider  the  func- 
tion of  the  water-soluble  vitamine  analogous  to  that  of 
secretine.  In  applying  this  hypothesis  to  scurvy  it  must 
be  borne  in  mind  that  the  sequence  may  be  reversed,  that 
the  lack  of  vitamine  may  not  lead  to  the  gastric  achylia, 
but  that  the  achylia  may  come  about  secondarily  as  the 
result  of  the  malnutrition. 

We  have  referred  to  "irregularities"  in  the  course  of 
the  "deficiency  diseases."  A  careful  perusal  of  the 
literature  leaves  one  with  the  impression  that  the  most  ex- 
perienced observers  are  not  entirely  satisfied  with  the 
exclusively  etiologic  relationship  of  the  vitamine  to  its 
respective  nutritional  disorder.  In  regard  to  scurvy,  more 
particularly,  there  are  numerous  scattered  reports  where 
the  disorder  did  not  yield  to  antiscorbutic  foods  as  might 


THE  ANTISCORBUTIC  VITAMINE  79 

have  been  expected,  or  where,  on  the  other  hand,  it  sud- 
denly and  inexplicably  retrogressed,  although  there  had 
been  no  alteration  in  the  dietary.6  These  instances  are  not 
common,  but  they  occur  from  time  to  time,  and  their 
occurrence  must  be  accounted  for.  In  relation  to  beriberi 
and  avian  polyneuritis  improvement  of  this  kind  has  fre- 
quently been  explained  on  the  theory  of  a  sudden  mobilisa- 
tion of  vitamines  from  the  tissues.  There  is,  however, 
no  data  on  which  to  base  such  explanations,  and  it  may 
be  that  a  lack  of  parallelism  between  vitamine  intake  and 
the  clinical  course  may  be  due  at  times  to  processes  taking- 
place  in  the  alimentary  tract. 

The  fat-soluble  vitamine  has  been  termed  by  some  the 
growth  vitamine.  All  the  vitamines,  however,  are  closely 
associated  with  the  function  of  growth,  which  their  defi- 
ciency tends  to  inhibit.  In  the  chapter  on  symptomatol- 
ogy, it  will  be  pointed  out  that  infants  suffering  from 
scurvy  fail  to  grow  normally  both  in  length  and  in  weight. 
To  a  certain  extent  this  may  be  due  to  a  loss  of  appetite, 
which  is  one  of  the  characteristic  phenomena  accompany- 
ing the  scorbutic  condition.  On  the  other  hand,  this 
anorexia  may  be  secondary  and  not  primary  to  the  impair- 
ment of  the  growth  impulse,  which  may  lead  to  a  dysfunc- 
tion of  various  body  processes. 

It  is  of  little  value  to  look  ahead  and  try  to  foresee 
what  the  next  decade  will  bring  forth  in  regard  to  the 
nature  of  the  vitamines.  Investigation  has  broadened 
remarkably  during  the  past  few  years  and  now  embraces 
the  chemical  field — chemical  and  adsorption  methods,  the 

e  Neumann,  for  example,  writes  that  he  has  seen  at  least  four  children 
whose  condition  was  not  improved,  although  in  addition  to  the  milk,  they 
took  asparagus,  spinach,  and  other  vegetables  or  apple  sauce.  Some  years 
ago  we  had  a  similar  experience.  It  has  likewise  happened  that  infantile 
scurvy  did  not  recur,  although  the  diet  was  the  same  as  that  which  originally 
led  to  the  disorder. 


80  SCURVY:    PAST  AND  PRESENT 

large  realm  of  biology,  including  studies  in  physiology 
and  pharmacology;  and  recently  pathology  has  once  more 
been  called  upon  to  aid  in  the  solution  of  the  problem. 
Probably  additional  vitamines  will  be  discovered.  From 
time  to  time  it  has  been  suggested  that  a  specific  growth 
vitamine  exists  quite  distinct  from  the  three  which  are 
recognized,  and  recently  Mellanby  has  suggested  still  an- 
other food  factor — a  specific  ' '  rachitic  vitamine. ' '  When 
we  reflect  that  the  characteristic  functions  of  the  various 
organs — the  kidneys,  liver,  etc. — nmst  depend  on  essential 
differences  in  chemical  structure,  the  complexity  of  the 
entire  problem  of  unidentified  factors  becomes  evident.7 

7  For  recent  and  comprehensive  reviews  of  the  vitamines  the  reader  is 
referred  to  papers  by  A.  B.  Macallum  (Trans.  Royal  Canadian  Institute, 
Toronto,  1919)  and  by  W.  H.  Eddy  (Abstracts  of  Bacteriol.  1919, 
Vol.  iii,  313.) 


CHAPTER  IV 
PATHOLOGY 

Physicians  have  had  a  general  knowledge  of  the 
pathology  of  scurvy  for  a  great  many  years.  Lind,  in 
his  " Treatise  on  the  Scurvy,"  published  in  1772,  included 
a  chapter  on  "  dissections  "  and  a  postscript  on  "  Appear- 
ances on  Dissections  of  Scorbutic  Bodies,"  based  on 
a  large,  although  indefinite,  number  of  postmortem  ex- 
aminations. In  the  century  which  followed,  there  are  to  be 
found  many  reports  of  scurvy,  especially  in  connection 
with  the  frequent  wars,  but  it  is  surprising  how  little 
detailed  pathologic  information  they  furnish.  Barlow's 
publication  in  1883,  establishing  the  identity  of  the  scurvy 
of  adults  and  of  infants,  must  be  regarded  as  the  modern 
milestone  in  the  study  of  the  pathology  of  this  disorder. 
This  work  did  not  contribute  richly  to  the  data  of  the 
subject,  or  suggest  novel  interpretations,  but  directed 
attention  to  a  new  source  of  material — the  increasing  num- 
ber of  cases  of  infantile  scurvy — at  a  critical  moment 
when  the  opportunity  for  the  study  of  scurvy  in  the  adult 
was  rapidly  becoming  less.  At  the  time  of  Barlow's  ex- 
position of  the  true  nature  of  " acute  rickets,"  scientific 
medicine  was  concentrating  its  interest  on  pathology. 
Tissues  were  being  carefully  studied  by  means  of  the 
microscope,  and  scurvy  was  subjected  to  this  new  method 
of  investigation.  As  a  result  of  intensive  application  of 
this  technic,  a  lesion  of  the  bones  was  identified  and  estab- 
lished as  characteristic  of  scurvy.  Study  was  focussed  so 
exclusively  on  the  bones,  that  for  many  years,  indeed  until 
very  recently,  the  other  organs  of  the  body  were  neglected. 

6  81 


82 


SCURVY:    PAST  AND  PRESENT 


This  is  true  of  the  gross  as  well  as  of  the  microscopic 
anatomy.  Protocol  after  protocol  gives  a  hasty  account 
of  the  appearance  of  the  various  organs,  merely  as  a 
routine  introduction  to  a  careful  and  often  minute  study 
of  the  bones  (Table  2) .  As  the  result  of  this  myopic  vision, 


TABLE  2 
Necropsy  Reports  of  Scurvy 


Many 
51 

8 

7 

7 
13 

2 

1 
23 

1 
3 
1 
1 
1 
2 
1 
1 
3 
1 

1 
1 
5 
1 
1 
1 
1 
1 

22 
1 
3 
1 

31 
1 


Lincl 

von  Himmelstein. . . 

Hayem 

Laseque  &  Legroux 

Charpentier 

Sato  &  Nambu 

Urizio 

Feigenbaum 

AschofT  &  Koch 


Smith 

Barlow 

MacKenzie . . . 
Northrup 

Cassel 

Sutherland . .  . 

Reinert 

Hirschsprung , 

Meyer 

Baginsky 


Naegeli 

Manz 

Schoedel  &  Nauwerk 

Jacobsthal 

Stoos 

Looser 

Hoffmann 

Stoeltzner 

Fraenkel 

Nob6court  et  al . . . . 

Ingier 

Bahrdt  &  Edelstein 

Erdheim 

Epstein 


1772 
1843 
1871 
1871 
1871 
1908 
1917 
1917 
1919 

Infants 

1876 
1883 
1883 
1892 
1893 
1894 
1895 
1896 
1896 
1897 

1897 
1899 
1900 
1900 
1903 
1905 
1905 
1906 
1908 
1913 
1913 
1913 
1918 

1918  . 

I 


Adults 

Brief  summaries 
Brief  summaries 
Resume 
Fairly  detailed 
Brief  summaries 
Fairly  detailed 
Brief  summaries 
Brief  summary 
Very  complete 

and  Children 


Brief  report 
Fairly  detailed 
Brief  summary 
Brief  report 
Brief  report 
Fairly  detailed 
Very  complete 
Summary 
Fairly  detailed 
Fairly  detailed 

Fairly  detailed 
Summary 
Very  complete 
Very  complete 
Fairly  complete 
Summary 
Summary 
Bone  only 
Resume" 
Brief  report 
Brief  report 
Complete 
Brief  summaries 
Very  detailed 


Brief  r£sume\ 


Fairly  detailed. 
Brief  summaries. 
Brief  summary. 
Very  complete. 


Bones,  brief  report. 


Brain  and  liver,  1  case. 
Fairly  complete. 


Brief,  bones  more  in 

detail. 
Bones  only. 

Very  complete. 
Very  complete. 
Bones  only. 

Bones  only. 

Bone  only. 

Bones  only. 

Bone  only. 

Bones,  very  complete. 

Bones,  brief  report. 

Brief  r6sume\ 


PATHOLOGY  83 

enlargement  of  the  heart,  for  example,  which  should  have 
been  noted  many  years  ago,  was,  until  recently,  unob- 
served— indeed,  the  heart  is  but  occasionallv  mentioned 
in  the  protocols. 

A  new  era  in  the  pathology  of  scurvy  was  inaugurated 
by  the  availability  of  experimental  scurvy  and  also  by 
the  stimulation  occasioned  by  the  recent  conception  of 
vitamines  and  the  so-called  deficiency  diseases.  In  en- 
deavoring to  elucidate  this  fascinating  problem,  it  has 
gradually  been  realized  that  pathology  may  be  of  service — 
for  example,  in  relation  to  the  involvement  of  the  endo- 
crine glands.  Accordingly,  studies  of  the  minute  pathol- 
ogy of  the  various  organs  have  been  undertaken  in  many 
laboratories  throughout  the  world  (Italy,  India,  England, 
Germany  and  the  United  States) .  An  additional  stimulus 
to  investigation  in  pathology  has  been  furnished  by  the 
recent  war,  which,  as  shown  elsewhere,  led  to  a  great 
increase  in  scurvy  among  both  the  military  and  civilian 
population.  The  excellent  report  of  Aschoff  and  Koch 
from  Roumania  was  made  possible  by  this  catastrophe, 
and  will  no  doubt  soon  be  followed  by  others  of  simi- 
lar character. 

Gross  Pathology. — General  Appearance. — The  skin  usually 
is  pale,  livid,  and  dotted  with  numerous  petechiae.  These 
vary  in  size  from  the  tiniest  pin-points,  barely  recog- 
nizable to  the  naked  eye,  to  ecchymoses  of  moderately 
large  size.  The  most  frequent  site  is  the  lower  extremi- 
ties. The  trunk  is  always  less  affected,  hemorrhages 
tending  to  occur  along  the  mid-line  and  especially  around 
the  umbilicus.  There  may  be  also  larger  superficial 
hemorrhages,  showing  great  differences  in  color,  from  the 
redder  tone  of  the  more  recent,  to  the  blues,  browns 
and  greens  of  the  older  lesions.    Bleeding  from  the  nose 


84     -  SCURVY:    PAST  AND  PRESENT 

and  mouth  is  not  uncommon  in  fatal  scurvy,  and  occasion- 
ally exophthalmos  is  present,  usually  unilateral,  and  due 
to  subperiosteal  hemorrhage  of  the  orbital  plate  of  the 
frontal  bone.  Rigor  mortis  is  generally  slight,  and, 
according  to  Lind  and  to  von  Opitz,  decomposition  takes 
place  rapidly. 

There  may  be  great  emaciation,  especially  where  sec- 
ondary infection  has  supervened.  General  wasting  occurs, 
however,  in  uncomplicated  scurvy  due  to  starvation — the 
result  of  lack  of  appetite  or  a  deficiency  of  the  general 
food  supply.  Children,  especially  infants,  are  undersized, 
as  illustrated  in  treating  of  the  symptomatology,  and  their 
bones  may  be  decidedly  smaller  than  normal.  Generally 
there  is  some  oedema  about  the  ankles,  and  in  children  a 
somewhat  characteristic  puffiness  about  the  eyes.  General 
anasarca  also  occurs,  in  some  cases  associated  with  renal 
involvement.  Peculiar  boggy,  "  tumor-like ' '  masses  of 
localized  edema  may  be  present,  which  were  considered 
by  the  earlier  writers  (Lind)  to  be  one  of  the  typical 
lesions  of  this  condition. 

Hemorrhages. — Hemorrage  is  such  a  striking  mani- 
festation that  it  is  not  surprising  to  find  it  was  regarded 
by  the  older  writers  as  the  pathognomonic  sign  of  scurvy. 
The  bleeding  may  take  place  into  almost  any  organ,  and 
vary  from  small  petechiae  to  very  extensive  extravasations. 
The  hair  follicles  and  sweat  glands  are  particularly  sus- 
ceptible, as  Laseque  and  Legroux  noticed  in  cases  occur- 
ring in  the  French  prisons.  Aschoff  and  Koch,  during  the 
recent  war,  noted  the  same  peculiarity  of  involvement,  call- 
ing attention  also  to  the  fact  that  previous  skin  diseases 
such  as  keratosis  or  seborrhea  seemed  to  predispose  to 
this  localization. 

Trauma  plays  a  very  important  role  in  determining 


PATHOLOGY  85 

the  location  of  the  deeper  as  well  as  of  the  superficial 
hemorrhages.  In  adults,  especially  in  soldiers,  in  whom 
the  greater  number  of  cases  have  been  recorded,  the  lower 
extremity  is  the  commonest  site,  between  the  knee  and 
ankle,  the  area  most  exposed  to  blows  as  well  as  acted 
upon  by  static  congestion.  In  infants,  the  inner  aspect  of 
the  thighs  is  a  frequent  site  due  to  the  trauma  of 
the  diaper. 

The  most  characteristic  hemorrhage,  the  subperiosteal, 
will  be  fully  discussed  when  considering  the  bone  lesions. 
The  deeper  hemorrhages  may  be  very  extensive.  They 
tend  to  follow  the  connective-tissue  strata,  and  in  the 
muscles  are  usually  limited  by  the  muscle  sheaths.  The 
blood  surrounds  the  muscle  fibres,  which  appear  quite 
intact.  The  neighboring  blood-vessels  are  congested  and 
may  contain  thrombi,  both  venous  and  arterial.  Such 
thrombi  are  found  also  in  areas  where  extravasation  has 
not  taken  place,  and  conversely,  hemorrhages  occur  where 
no  thrombi  are  demonstrable,  so  that  a  mutual  causal 
relationship  cannot  be  proved.  Further  evidence  in  re- 
gard to  the  mechanism  of  these  extravasations  is  pre- 
sented in  the  discussion  of  the  minute  anatomy.  Brownish 
pigment,  undoubtedly  derived  from  the  blood,  is  fre- 
quently found  in  the  neighborhood  of  the  hemorrhagic 
areas.  New  connective  tissue  also  grows  in  these  areas, 
so  that  in  healing  cases  a  marked  formation  of  scar  tissue 
will  be  found.  Bizarre  forms  of  hemorrhage  at  times 
have  given  rise  to  confusion  in  diagnosis ;  hemorrhage  in- 
volving the  right  lower  abdominal  quadrant  may  simulate 
appendicitis;  when  occurring  in  the  region  of  the 
transverse  colon  it  has  been  mistaken  for  an  epi- 
gastric new-growth. 

Certain  parts  of  the  body  seem  less  predisposed  to 


86  SCURVY:    PAST  AND  PRESENT 

hemorrhage.  The  central  nervous  system  is  often  spared, 
notwithstanding  extensive  bleeding  elsewhere,  the 
meninges  being  somewhat  more  frequently  involved. 
Hemorrhage  of  the  lungs  is  also  less  common  than  might 
be  expected,  and  it  is  probably  true  as  Laseque  and  Le- 
groux  suggested,  that  previous  pulmonary  disease,  par- 
ticularly tuberculosis,  is  an  important  predispos- 
ing factor.     •  k.,j 

Anasarca. — This  comprises  the  second  characteristic 
lesion  found  in  scurvy  at  necropsy  and  was  referred  to 
in  the  earliest  records  of  the  disease.  In  the  account 
of  his  dissections  Lind  writes :  ' '  The  breast,  belly  and 
several  other  parts  of  the  body  were  filled  with  this  water 
or  serum, ' '  mentioning  also  the  pericardium  and  ventricles 
of  the  brain.  He  also  noted  that  all  the  tissues  seemed  to 
contain  an  excessive  amount  of  fluid,  a  condition  which 
may  be  so  striking  that  the  muscles  appear  bathed  in 
seruni.  In  one  of  his  first  cases  with  postmortem  verifica- 
tion, Barlow  described  this  appearance  as  follows:  "The 
muscular  walls  of  the  thorax  were  pale  yellow  and  watery, 
as  though  they  had  been  bathed  in  serum. ' '  In  many  cases 
this  edema  is  most  marked  in  the  neighborhood  of  the 
hemorrhages,  for  example,  in  the  muscles  of  the  thigh 
when  subperiosteal  hemorrhage  has  taken  place;  less 
frequently  it  is  produced  by  venous  thrombosis. 

Any  or  all  of  the  serous  cavities  may  be  involved  in 
this  hydrops,  the  order  of  frequency  being  pericardium, 
pleura?,  peritoneum,  and  joint  surfaces,  especially  the 
knee.  The  fluid  is  clear  and  straw-colored,  or,  in  the  event 
of  secondary  infection,  becomes  cloudy  and  fibrino-puru- 
lent.  Later  the  exudate  may  become  organized  so  that  the 
entire  cavity  is  filled  with  a  solid  mass,  which  binds  the 
organs  together  and  obliterates  the  cavity.   The  exudate 


PATHOLOGY  87 

may  be  blood-stained  or  apparently  consist  entirely  of 
clotted  blood. 

Heart. — In  the  protocols  of  most  necropsies,  the  heart 
is  passed  over  with  scant  mention.  For  example,  Lind's 
only  statement  in  this  regard  is  that  "all  those  who  died 
suddenly,  without  any  visible  cause  of  their  death,  had  the 
auricles  of  their  heart  as  big  as  one's  fist,  and  full  of 
coagulated  blood.' '  Barlow  accords  it  no  attention,  nor 
do  most  of  the  writers  who  immediately  followed  him. 
The  first  careful  description  of  the  heart  is  to  be  found 
in  the  excellent  work  of  Schoedel  and  Nauwerk,  which 
contains  the  following  record  in  regard  to  three  of  the 
five  necropsies  on  infantile  scurvy:  (1)  Pericardial  fluid 
somewhat  increased,  both  ventricles  moderately  dilated, 
the  right  somewhat  hypertrophic.  (2)  The  heart  showed 
a  hypertrophy  of  the  right  and  left  ventricles,  as  well  as 
dilatation  of  the  right  ventricle.  (3)  The  right  ventricle 
is  dilated  and  slightly  hypertrophied,  the  muscles  pale 
and  tough.  There  is  no  word  of  comment  relative  to  these 
cardiac  changes,  which  evidently  were  considered  fortui- 
tous. The  same  observation  holds  true  in  regard  to  a 
necropsy  on  an  eight-year-old  child  reported  by  Ingier, 
which  showed  a  moderate  hypertrophy  of  the  left  ven- 
tricle. We  look  in  vain,  likewise,  for  information  on  the 
subject  in  the  work  on  guinea-pig  scurvy  by  Hoist  and 
Froelich,  and  that  on  scurvy  in  the  monkey  by  Hart  and 
Lessing.  The  first  linking  of  cardiac  enlargement  with 
scurvy  is  found  in  a  paper  by  Darling,  who  described 
"right-sided  hypertrophy  and  degenerative  changes  in  the 
vagus  and  all  its  branches."  Hess  described  and  demon- 
strated by  means  of  roentgenograms  the  enlarged  heart  in 
infantile  scurvy.  Recently  Erdheim,  in  an  article  en- 
titled "Das  Barlowherz,"  reported   the   occurrence   of 


88  SCURVY:    PAST  AND  PRESENT 

enlargement  of  the  heart,  especially  of  the  right  ventricle, 
in  21  out  of  31  necropsies  of  infantile  scurvy,  and  con- 
cluded that  a  direct  ratio  exists  between  the  degree  of 
enlargement  and  the  intensity  of  the  disorder.  These 
reports  gain  added  interest  in  view  of  the  enlargement  of 
the  right  heart  so  frequently  encountered  in  beriberi,  and 
described  by  Andrews  in  infants  dying  of  this  condition. 
In  addition  to  the  definite  statement  of  Darling  regarding 
adults,  mention  may  be  made  of  the  observation  of 
Aschofx*  and  Koch,  that  in  two  cases  of  uncomplicated 
scurvy  there  were  fatty  degeneration  and  dilatation  of 
the  heart.  Fatty  degeneration  of  the  muscle  is  frequent, 
brown  atrophy  exceptional.  Sato  and  Nambu  also  found 
hyperemia  and  atrophy  with  increase  of  connective  tissue 
between  the  muscle  fibres. 

The  pericardial  cavity  contains  almost  invariably  an 
increased  quantity  of  fluid,  which  may  be  so  great  as  to 
impede  the  heart 's  action.  Adhesive  pericarditis  has  been 
described.  The  cardiac  valves  are  normal,  unless  pre- 
viously damaged. 

Lungs. — The  lungs  are  almost  always  congested,  but 
apart  from  this  are  remarkably  free  from  abnormality. 
Smaller  or  larger  hemorrhages  are  described  occasionally, 
which  are  usually  considered  truly  scorbutic;  Andrews, 
however,  found  similar  lesions  in  beriberi.  In  the  ne- 
cropsy of  Stephen  Mackenzie's  case,  described  by  Barlow, 
these  small  hemorrhages  are  stated  to  have  resembled 
small  red  tubercles  scattered  throughout  the  lung.  There 
may  be  pulmonary  infarcts.  Edema  of  the  lungs  is  not 
uncommon,  as  we  should  expect,  especially  as  a  terminal 
condition.  Pneumonia,  lobular  or  lobar,  is  one  of  the  most 
frequent  complications  and  causes  of  death.  Active  tuber- 
culosis is  a  not  uncommon  secondary  manifestation. 


PATHOLOGY  89 

Subserous  hemorrhages  are  almost  the  rule ;  if  infec- 
tion supervenes,  the  pleurae  become  thickened  and  covered 
with  an  exudate  of  pus  and  fibrin. 

Alimentary  Tract. — The  lesions  of  the  gums  so  well 
recognized  clinically  are  fully  discussed  under  symptoma- 
tology. The  remarkable  fact  that  these  hemorrhages  do 
not  appear  in  edentulous  gums  has  been  the  centre  of 
the  controversy  as  to  the  identity  of  adult  scurvy  and 
Barlow's  disease.  This  same  lack  of  involvement  is  noted 
in  adults  whose  teeth  have  been  extracted.  Where  teeth 
are  present,  the  gums  are  swollen  and  edematous,  often 
of  a  livid,  reddish  color;  less  frequently,  pale  and  pouting. 
Hemorrhage  is  seen  at  the  edge  of  the  gum  adjacent  to  the 
teeth.  In  advanced  cases  the  gums  are  enormously  swol- 
len, fungous,  ulcerated  and  covered  with  a  foul,  greenish, 
necrotic  mass,  which  may  extend  widely  over  the  buccal 
mucous  membrane.  The  teeth  become  loosened  and  fall 
out.  Secondary  infection  undoubtedly  plays  the  chief  role 
in  producing  this  condition,  for  the  most  severe  forms  are 
found  only  where  caries  and  pyorrhoea  preexisted.  This 
seat  of  infection  may  serve  as  the  source  of  dissemination 
throughout  the  body,  giving  rise  to  many  of  the  lesions 
found  at  postmortem,  especially  in  the  lower  part  of 
the  intestinal  tract. 

The  stomach  shows  no  characteristic  changes.  Con- 
gestion of  the  mucosa  is  frequent,  at  times  associated  with 
small  superficial  erosions ;  the  latter  gain  added  interest 
in  view  of  their  occurrence  in  guinea-pig  scurvy.  Hemor- 
rhages occur  here  also  and  may  involve  any  of  the 
mural  coats. 

The  duodenum  shows  often  intense  congestion.  This 
occurs  with  sufficient  frequency  to  demand  attention,  espe- 
cially as  a  similar  condition  has  been  described  in  other 


90  SCURVY:    PAST  AND  PRESENT 

disorders  grouped  with  scurvy.  Willcox  and  others  found 
congestion  of  the  duodenum  and  of  the  lower  intestine  in 
beriberi,  and  Andrews  described  not  only  congestion  but 
even  minute  hemorrhages.  Small  duodenal  ulcers  are  by 
no  means  infrequent  both  in  human  and  in  guinea-pig 
scurvy  (Hoist  and  Froelich).  The  presence  of  such 
markedcongestion  surrounding  the  papilla  of  Vlater  would 
lead  us  to  expect  the  occurrence  of  catarrhal  jaundice 
associated  with  scurvy.  But,  on  the  contrary,  icterus 
has  rarely  been  noted  in  scurvy.  Urizio  has  described 
jaundice  in  this  connection,  but  it  is*  difficult  to  decide 
whether  his  cases  were  true  scurvy,  as  they  occurred  in 
an  epidemic  of  jaundice  and  no  histologic  examination 
of  the  bones  was  carried  out. 

The  intestine  may  present  a  variety  of  lesions.1  The 
mucosa  is  frequently  congested  and  swollen,  and  the  soli- 
tary follicles  and  Peyer  's  patches  enlarged.  These  changes 
may  progress  to  necrosis  and  extensive  ulceration.  In  an 
outbreak  of  scurvy  occurring  in  this  country  in  1917,  in  a 
large  institution  for  epileptics,  ulceration  was  a  frequent 
lesion  at  necropsy.2  Dysentery,  a  frequent  complication 
of  scurvy  in  some  epidemics,  may  add  to  this  ulceration 
and  lead  to  even  complete  sloughing  of  the  inner  lining  of 
the  intestine.  Hemorrhages  are  found  in  the  mucous, 
serous  or  muscular  layers.  Here,  as  elsewhere,  the 
hemorrhages  vary  in  size  from  petechia}  to  large  miiltra- 
tions  of  blood.    A  very  striking  picture  is  sometimes  pre- 

1  For  details  regarding  the  intestinal  lesions  in  infantile  scurvy,  the 
reader  is  referred  to  Barlow's  description  of  the  case  of  Stephen  Mackenzie, 
to  one  necropsy  report  by  Theodor  Fischer,  one  by  Hirschsprung,  one  by 
\I<-yer,  and  five  by  Schoedel  and  Nauwerk.  The  prevailing  lesions  are 
hemorrhages,  pigmentation,  follicular  ulceration,  and  enlargement  of  the 
mesenteric  glands. 

3  The  potato  crop  largely  failed  this  year,  and  there  was  considerable 
scurvy  in  the  spring,  as  described  in  the  chapter  on  antiscorbutics. 


PATHOLOGY  91 

sentecl  by  the  pale,  edematous  intestinal  wall  dotted  or 
streaked  with  vivid  red. 

Liver. — The  liver  is  frequently  congested,  as  would  be 
expected  in  view  of  the  involvement  of  the  right  heart. 
Erdheim  found  congestion,  however,  in  only  nine  among 
thirty-one  necropsies,  although  enlargement  of  the  heart 
was  present  twenty-one  times.  There  may  be  hemor- 
rhages in  the  glandular  tissue  or  under  the  peritoneum. 
"  Clou dy"  and  fatty  degenerations  occur  occasionally,  and 
in  some  cases  an  early  cirrhosis.  Lind  found  abscess  of 
the  liver,  and  wrote1  that  in  a  few  instances  ' '  the  matter  or 
corruption  was  hardened,  as  it  were,  into  a  stone. ' ' 

Spleen. — This  organ  is  usually  somewhat  enlarged  and 
congested.  Charpentier,  in  the  Paris  epidemic  of  1871, 
found  it  often  three  to  four  times  the  normal  size  and  very 
soft,  and  Lind  tells  us  that  "the  spleen  was  three  times 
bigger  than  natural,  and  fell  to  pieces,  as  if  composed 
of  congealed  blood/ '  It  must  be  remembered  that  the 
pathologic  as  well  as  the  clinical  picture  of  the  scurvy 
of  Lind  and  his  time  was  generally  complicated  by  infec- 
tion. The  enlargement  is  usually  by  no  means  so  great, 
and  no  doubt  is  due  in  part  to  intercurrent  infections.  On 
section,  it  is  found  frequently  to  contain  much  reddish- 
brown  pigment.  Hemorrhage  may  also  occur.  In  beri- 
beri, Andrews  observed  frequent  congestion  of  the  spleen 
and  also  a  loss  of  normal  markings. 

Pancreas. — There  is  but  one  reference  to  a  lesion  of  the 
pancreas  in  scurvy,  that  of  Sato  and  Nambu,  who  encoun- 
tered hemorrhage  of  this  organ  in  one  case  among  the 
necropsies  performed  in  the  course  of  the  Russo-Japan- 
ese War. 

Kidneys. — Here  again,  congestion  and  hemorrhage  are 


92  SCURVY:    PAST  AND  PRESENT 

the  two  lesions  most  commonly  found.  The  kidneys  also 
may  show  any  of  the  forms  of  nephropathy  ordinarily 
recognized,  but  these  must  be  regarded  as  complicating 
conditions  and  not  a  part  of  the  true  scurvy. 

Small  hemorrhages  may  be  found  in  the  uterus,  blad- 
der or  urethra.  They  are  especially  common  in  the  blad- 
der, both  in  man  and  in  the  guinea-pig,  and  in  some 
instances  may  be  the  cause  of  the  hematuria  noted  dur- 
ing life. 

Lymph-nodes. — General  enlargement  of  the  lymph- 
nodes  has  been  described,  but  occurs  probably  only  in 
advanced  cases  where  a  general  infection  has  been  super- 
added. As  a  rule  the  enlargement  is  confined  to  nodes 
draining  areas  where  hemorrhage  has  occurred.  On  sec- 
tion these  nodes  are  reddish  or  brownish  as  the  result 
of  the  pigment  which  they  contain,  the  "  black  and  red 
spots  of  different  sizes' '  mentioned  by  Lind.  Following 
infection  they  may  become  purulent,  resulting  in  the  in- 
guinal buboes  so  frequently  mentioned  by  the  older 
authors,3  or  in  the  purulent  mesenteric  nodes  associated 
with  intestinal  ulceration. 

Organs  of  Internal  Secretion. — Until  recently  these 
organs  have  received  but  little  attention.  It  is  probable, 
however,  that  in  the  near  future  they  will  be  the  object 
of  close  study  and  that  new  information  will  be  acquired 
as  to  their  condition  in  this  disorder.  Hemorrhages  are 
commonly  seen  in  the  adrenals,  enlarging  them  greatly  and 
giving  them  a  deep  red  color;  the  hemorrhage  generally 

8 Lind  writes:  "In  the  months  of  July  and  August  I  opened  near 
seventy  large  swellings  in  the  groin,  proceeding  entirely  from  scurvy."  .  .  . 
"  We  found  the  glands  under  their  arm-pits  much  enlarged  and  surrounded 
with  purulent  matter,  as  well  as  the  muscles  of  their  arms  and  thighs."  .  .  . 
"  The  glands  of  the  mesentery  are  generally  obstructed  and  swelled.  Some 
of  these  were  found  partly  corrupted  and  imposthumated." 


PATHOLOGY  93 

involves  mainly  the  medullary  portion.4  It  is  probable 
that  careful  scrutiny  will  disclose  hemorrhages  in  the  other 
glands  of  internal  secretion.  The  question  of  the  involve- 
ment of  these  glands  will  be  again  considered  under  the 
microscopic  anatomy,  and  has  been  taken  up  from  a  func- 
tional standpoint  in  treating  of  the  possible  indirect 
action  of  the  vitamines. 

The  brain  and  the  spinal  cord  likewise  have  been  but 
little  studied.  It  is  hardly  to  be  expected  that  much  will 
be  learned  from  an  investigation  of  the  gross  pathology 
of  these  organs,  but  the  microscopic  anatomy  offers  a 
promising  field  of  research.  Hemorrhage  may  occur  into 
the  brain  substance,  into  the  cord  or  the  membranes  sur- 
rounding them.  Pachymeningitis  hemorrhagica  interna 
has  been  described  frequently  (Meyer,  Hay  em,  Suther- 
land, Sato  and  Nambu)  and  may  give  rise  to  the  symp- 
toms of  meningitis.  Sutherland  reports  an  instance  where 
thrombosis  of  the  basal  artery  was  found  postmortem. 
In  one  case,  that  of  Feigenbaum,  hemorrhage  of  the  cord 
was  diagnosed  during  life  and  confirmed  at  necropsy. 

The  peripheral  nerves  may  be  the  seat  of  hemorrhages, 
the  blood  lying  between  the  nerve  trunk  and  its  sheath. 
This  is  particularly  well  illustrated  in  the  recent  work  of 
Aschoff  and  Koch. 

Bones. — Palpation  of  the  body  will  often  reveal  distinct 
lesion  of  the  bones,  such  as  fractures,  either  ununited  or 
healed  with  the  formation  of  large  calluses ;  subperiosteal 
hemorrhages,  especially  of  the  distal  end  of  the  femur 
or  of  the  tibia,  may  be  evident  to  the  eye  as  well  as  to 
the  touch.  Crepitation  of  the  bones  may  serve  to  further 
establish  the  break  in  continuity  of  the  bones.    This  lesion 

4  In  view  of  the  report  of  Hart  and  Leasing  of  calcium  deposits  in  the 
adrenal  glands  of  monkeys  suffering  from  scurvy,  special  attention  should 
be  given  to  this  point  in  necropsies  on  human  beings. 


94  SCURVY:    PAST  AND  PRESENT 

was  well  known  to  the  older  writers.  Lind  writes  that 
"in  some,  when  moved,  we  heard  a  small  grating  of  the 
bones.  Upon  operating  those  bodies  the  epiphyses  were 
found  entirely  separated  from  the  bones ;  which,  by  rub- 
bing against  each  other,  occasioned  this  noise."  "All  the 
young  persons  under  18  had  in  some  degree  their  epi- 
physes separated  from  the  body  of  the  bone,  this  water 
having  penetrated  into  the  very  substance  of  it. ' '  Poupart 
was  also  struck  by  this  phenomenon  in  young  adults. 

Another  bony  alteration  which  is  readily  palpable  is 
"beading"  of  the  ribs,  the  counterpart  of  the  rhachitic 
rosary.  This  has  not  been  considered  a  sign  of  scurvy, 
and  when  noted  clinically  or  at  postmortem  has  been 
passed  over  without  comment,  just  as  has  been  the  case 
with  cardiac  hypertrophy.  In  infants  the  beading  has 
been  attributed  to  rickets,  and  this  error  has  been  largely 
responsible  for  the  general  opinion  that  almost  all  infants 
suffering  from  scurvy  suffer  also  from  rickets.  If  we 
scan  the  literature  with  this  question  in  mind,  we  find 
numerous  casual  references  to  beading  of  the  ribs  in 
scurvy.  FraenkePs  frequently-cited  case  of  a  child  of 
seven  who  died  of  acute  scurvy,  showed  beading  of  the 
ribs  during  life  as  well  as  after  death.  The  true  scorbutic 
character  of  these  enlargements  was  substantiated  by 
microscopic  examination.  In  their  pathologic  studies  on 
scurvy  among  soldiers,  Aschoff  and  Koch  frequently  de- 
scribe beading  of  the  ribs,  which  they  attribute  to  an 
infraction  of  the  costochondral  junctions.5     There  may  be 

sThe  beading  may  have  the  usual,  rounded,  smooth,  knobby  character. 
There  may  be,  however,  what  one  might  term  "  angular  beading,"  the  junc- 
tion taking  on  a  steplike  form,  as  if  the  abutting  ends  of  the  cartilage  and 
the  bone  were  of  unequal  size  and  not  well  fitted  to  each  other.  The  carti- 
lage overtops  the  hone,  so  that  on  palpating  the  joint  there  is  a  precipitous 
fall  as  we  run  the  finger  outward  from  the  surface  of  the  cartilage,  or  a  sud- 
den elevation  on  palpating  the  rib  from  without  inward  toward  the  sternum. 


PATHOLOGY  95 

fracture  at  this  junction,  or  a  separation  of  the  cartilages 
from  the  sternum,  as  described  by  Lind. 

This  beading  of  the  ribs,  which  involves  mainly  the 
middle  tier,  was  described  by  Hoist  and  Froelich  in  their 
classic  report  of  guinea-pig  scurvy,  and  has  been  noted  by 
all  subsequent  investigators  in  this  field.  It  has  usually 
been  called  "rhachitic"  or  "pseudo-rhachitic"  in  spite  of 
the  fact  that  this  junction  is  the  site  of  typical  scorbutic 
microscopic  lesions.  Hart  and  Lessing  refer  to  the  "rha- 
chitic  rosary"  in  monkeys,  likewise  not  realizing  that 
it  is  the  product  of  scurvy. 

The  subperiosteal  hemorrhage  has  long  been  recog- 
nized as  a  lesion  characteristic  of  scurvy.6  It  occurs  ex- 
ceptionally in  the  upper  extremities,  and  most  commonly 
at  the  lower  end  of  the  femur ;  it  may,  however,  involve 
almost  any  of  the  bones,  and  has  been  described  in  connec- 
tion with  the  scapula,  cranial  vault,  orbital  plate  of  the 
frontal  bone,  ribs,  etc.  It  varies  greatly  in  its  size,  being 
confined  to  a  small  area  or  extending  a  long  distance  on 
the  shaft  of  the  bone.  It  rarely  is  as  large  as  one  would 
expect  from  external  appearance,  as  much  of  the  swelling- 
is  due  to  edema  and  hemorrhage  into  the  soft  parts.  The 
periosteum  rarely  becomes  separated  at  the  line  of  junc- 
tion of  the  epiphysis  and  diaphysis.  The  underlying 
blood  coagulates  rapidly,  and  the  periosteum  begins  to 
calcify  within  a  few  weeks,  as  shown  by  the  X-ray. 

The  most  frequent  site  of  fracture,  or  separation  of 

"There  seems  to  be  some  misconception  as  to  the  pathogenesis  of  the 
subperiosteal  hemorrhage  in  scurvy.  In  most  reports  this  lesion  is 
described  as  if  it  resulted  from  a  hemorrhage  burrowing  its  way  beneath 
the  periosteum  and  raising  it  from  the  subjacent  bone.  In  point  of  fact, 
such  an  event  is  impossible,  as  will  be  fully  realized  when  one  experiences 
the  great  difficulty  in  separating  periosteum  from  normal  bone.  Scurvy  in- 
volves a  periosteum  which  is  not  normal;  it  is  insecurely  attached  to  the 
shaft  of  the  bone,  so  that  it  is  readily  stripped  off  by  hemorrhage. 


96  SCURVY:    PAST  AND  PRESENT 

the  epiphysis,  is  the  lower  end  of  the  femur.  This  may  be 
accompanied  by  local  swelling,  or  be  discovered  at  ne- 
cropsy, or  during  life  by  means  of  the  X-ray  in  cases  in 
which  it  has  not  been  suspected.  An  interesting  fracture 
reported  by  the  author,  and  also  mentioned  by  Kaufmann 
and  by  Schoedel,  is  that  of  the  head  of  the  femur  leading 
to  the  development  of  coxa  vara.  In  the  author's  case,  the 
condition  was  found  in  a  scorbutic  infant  who  had  never 
stood  on  its  feet.  Schoedel  suggests  that  scurvy  may  at 
times  be  the  etiologic  factor  in  coxa  vara  as  well  as  in  some 
cases  diagnosed  as  congenital  dislocation  of  the  hip. 

On  sectioning  the  bones  longitudinally  the  cortex  is 
noted  to  be  exceedingly  thin,  a  mere  shell  and  very  brittle. 
The  trabecular  are  so  thin  and  reduced  in  number  that  the 
bone  has  become  a  very  fragile  structure.  The  marrow 
is  no  longer  deep  red  at  the  ends  of  the  long  bones,  but 
yellowish,  frequently  presenting  a  patchy  appearance. 
It  has  a  gelatinous  consistency.  This  ^G^eruestmark,,  is 
one  of  the  characteristic  anatomical  changes  of  scurvy, 
and  will  be  fully  described  in  considering  the  microscopic 
picture.  Hemorrhages  can  be  clearly  distinguished  in 
the  marrow,  and  are  of  varying  shades  denoting  their 
irregular  occurrence.  These  hemorrhages  were  consid- 
ered by  Looser  to  be  the  cause  of  the  connective-tissue  for- 
mation in  the  marrow,  but  do  not  occur  with  sufficient 
constancy  to  warrant  this  interpretation.  Moreover,  this 
"frame-work  marrow' '  is  found  where  there  is  no  evi- 
dence of  previous  hemorrhage. 

MICROSCOPIC  PATHOLOGY 

Skin. — As  pointed  out  by  Aschoff  and  Koch,  examina- 
tion of  skin  which  to  gross  appearance  was  the  seat  of 
typical  small  hemorrhages,  showed  various  lesions.    In 


PATHOLOGY  97 

some,  perhaps  the  most  typical  forms,  there  had  been  a 
fresh  extravasation  of  red  blood-ceils.  This  condition 
is  found  usually  in  the  subepidermal  layers,  especially  in 
the  papillary  stratum.  These  small  hemorrhages  occur 
very  frequently  about  the  hair  follicles  and  sweat-glands, 
especially  when  they  have  been  diseased.  Where  the 
bleeding  has  been  of  long  standing,  dark  brownish  pigment 
deposits  are  found  and  all  blood-cells  may  have  disap- 
peared. Phagocytic  cells  are  almost  always  present  and 
may  be  of  the  " wandering* '  or  of  the  more  fixed  connec- 
tive-tissue type.  Many  round  cells  may  be  seen  in  these 
areas  lying  between  the  connective-tissue  strands  or 
around  the  blood-vessels.  Rheindorf ,  as  quoted  by  Tuech- 
ler,  has  called  attention  to  this  round-celled  reaction, 
which  in  many  instances  gives  a  picture  analogous  to  the 
granulomas,  and  which  leads  him  to  infer  an  infectious 
origin  for  these  lesions.  Other  areas  which  appeared  to 
be  the  seat  of  hemorrhage  are  shown  by  the  microscope  to 
be  small  abscesses  or  new  connective  tissue  often  loaded 
with  pigment  and  detritus,  apparently  representing  the 
final  stage  of  these  lesions.  Aschoff  and  Koch  have  found 
that  suitably-stained  preparations  frequently  show  a  loss 
of  elastic  fibres,  which  Rheindorf  states  constitutes  one  of 
the  earliest  changes  of  this  disorder.  The  blood-vessels 
in  the  vicinity  of  the  hemorrhages  are  congested,  espe- 
cially the  capillaries  and  small  venules. 

The  muscles  also  present  a  similar  diverse  picture 
of  old  and  recent  hemorrhages,  pigment  deposit  and 
round-celled  infiltration.  Increase  of  connective  tissue  is 
usually  found  between  the  fibre  bundles  and  in  some  cases 
where  the  hemorrhages  are  apparently  of  long  standing, 
as  evidenced  by  loss  of  contour  of  the  red  cells  and  pig- 
mentation of  the  surrounding  areas,  this  scar  tissue  for- 
7 


98  SCURVY:    PAST  AND  PRESENT 

ination.is  very  marked.  Changes  in  the  muscle  fibres 
themselves  have  not  been  encountered  by  all  observers. 
Hayem  describes  widespread  fatty  degeneration  and  a 
deposit  of  pigment  within  the  fibres,  Leven  a  loss  of  sarco- 
lemma,  while  Laseque  and  Legroux  found  fatty  changes 
which  were  equally  marked  in  muscles  showing  no  hemor- 
rhage. On  the  other  hand,  Aschoff  and  Koch,  in  their 
careful  studies,  did  not  find  noteworthy  fatty  change  of  the 
fibres,  but  observed  often  that  the  fibres  within  the  hemor- 
rhagic areas  seemed  shrunken  and  were  stained  abnor- 
mally deep  with  eosin. 

In  monkeys  dying  of  experimental  scurvy,  Hart  and 
Lessing  describe  granules  in  the  muscles,  which,  judged 
by  their  staining  affinities,  evidently  contained  calcium  and 
were  similar  to  those  found  in  the  adrenal  glands. 

Blood-vessels. — A  similar  difference  of  opinion  obtains 
in  regard  to  the  changes  in  the  walls  of  the  blood-vessels, 
especially  of  those  in  hemorrhagic  areas.  This  question  is 
of  particular  interest  because  of  its  bearing  on  the  prob- 
lem of  the  mechanism  involved  in  the  escape  of  the  blood. 
Since  it  has  been  demonstrated  that  neither  the  clotting 
time  nor  the  viscosity  of  the  blood  is  markedly  changed 
in  scurvy  but  that  weakness  of  the  vessel  walls  exists,  as 
demonstrated  by  "the  capillary  resistance  test,"  it  is 
natural  that  we  should  seek  an  explanation  in  the  micro- 
scopic pathology  of  the  vessels.  So  far  no  change  has 
been  found.  The  application  of  some  of  the  newer  stains, 
such  as  those  for  mitochondria  and  other  cell  granules, 
has  not  been  resorted  to  for  this  study,  and  might  fur- 
nish valuable  information. 

Hayem  found  fatty  infiltration  of  the  walls  of  the  small 
veins  and  capillaries,  and  believed  this  to  play  an  import- 
ant role  in  the  etiology  of  these  bleedings.   Laseque  and 


PATHOLOGY  99 

Legroux  also  found  occasional  fatty  changes.  Other 
authors  have  failed  to  demonstrate  similar  lesions,  or  have 
considered  them  due  to  postmortem  change.  Koch 
searched  in  vain  for ' l  rents ' '  in  the  vessel  walls  to  account 
for  the  escape  of  blood.  Hyaline  degeneration  has  also 
been  described,  but  is  believed  to  result  from  secondary 
infections  and  not  to  be  an  intrinsic  lesion  of  scurvy 
(Sato  and  Nambu,  Aschoff  and  Koch). 

Thrombosis  of  vessels  is  found  both  in  the  neighbor- 
hood of  hemorrhage  and  elsewhere,  the  thrombi  at  times 
completely  occluding  the  vessels  and  giving  rise  to  typical 
wedge-shaped  infarcts.  The  lung  often  shows  areas  of 
this  kind. 

Lungs. — Hemorrhages  of  various  size  occur  in  the  tis- 
sue of  the  lung  or  in  the  air  spaces.  Hemorrhagic  infarcts 
also  have  been  described,  and  Sato  and  Nambu  report 
hyaline  degeneration  of  the  blood-vessel  walls.  Secondary 
pneumonias,  usually  broncho-pneumonic  in  type,  are  of 
common  occurrence,  and  in  many  epidemics  constitute  the 
prevailing  cause  of  death.  Tuberculous  lesions  are  also 
frequently  present,  and  are  stated  to  assume  fresh  activ- 
ity as  the  result  of  the  nutritional  disorder.  Edema 
occurs  frequently,  the  fluid  in  the  acini  often  containing 
red  blood-cells.  Subpleural  hemorrhages,  thickening  of 
the  pleura,  purulent  or  fibrinous  pleurisy  are  com- 
mon lesions. 

Heart. — Although  hypertrophy  and  dilatation  of  the 
heart  have  been  noted  by  several  observers,  microscopic 
changes  have  rarely  been  recorded.  Meyer,  and  also 
Leven,  report  fatty  degeneration  of  the  muscle  fibres, 
which,  however,  was  found  by  Aschoff  and  Koch  in  only 
one  case.    Sato  and  Nambu  described  an  increase  of  con- 


100  SCURVY:    PAST  AND  PRESENT 

nective  tissue,  and  others  anemia  and  pigmentation. 
Thickening  of  the  pericardium  and  subserous  hemor- 
rhages also  occur. 

ALIMENTARY  TEACT 

Gums. — Where  it  has  been  possible  to  examine  the 
gums  of  early  cases,where  swelling,  redness  or  bluish  dis- 
coloration are  the  chief  symptoms  and  before  secondary 
infection  has  set  in,  the  microscopic  picture  is  very  similar 
to  that  of  the  skin.  Small  hemorrhages,  round-celled  in- 
filtration, increase  of  connective  tissue,  clumps  of  pig- 
ment containing  cells,  or  a  diffuse  deposit  of  brownish 
granules  complete  the  picture.  Congestion  and  edema 
are  usually  evident.  The  changes  are  most  pronounced 
in  the  deeper  layers  of  the  submucosa  and  about  the 
muscles,  leaving  the  superficial  layers  strikingly  intact, 
beneath  an  apparently  normal  epithelium.  In  the  later 
stages,  erosion  of  the  mucosa  occurs,  and  the  upper  layers 
of  submucosa  become  involved.  Polynuclear  cells  appear 
in  great  numbers,  abscesses  and  ulcers  are  formed,  which 
with  proper  staining  can  be  shown  to  harbor  the  various 
types  of  mouth  bacteria,  cocci,  spirillar,  etc.  The  pigmen- 
tation becomes  intense,  and  a  marked  increase  of  the 
newly-formed  connective  tissue  takes  place. 

The  lesions  of  the  stomach  are  neither  characteristic 
nor,  as  a  rule,  very  striking.  Hemorrhages  occur,  the 
larger  ones  generally  in  the  subperitoneal  layers,  the 
smaller  ones  in  any  of  the  coats.  Thickening  of  the  wall 
follows  or  accompanies  these  hemorrhages.  Superficial 
erosions  of  the  mucosa  or  even  ulcers  may  be  seen. 

The  striking  congestion  of  the  duodenum  has  been  fully 
discussed  in  considering  the  gross  pathology.  At  any  level 
in  the  intestinal  tract  hemorrhage  may  take  place,  with  the 


PATHOLOGY  101 

resulting  pigmentation  and  scar-tissue  formation.  The 
lymphoid  structures — solitary  follicles  and  Peyer's 
patches — are  usually  intensely  congested  and  often  the 
seat  of  hemorrhage.  They  constitute  the  sites  of  predilec- 
tion for  ulcerative  processes  of  the  gut.  Bacteria  can  be 
demonstrated  at  times  in  the  submucous  layers;  how- 
ever, no  type  has  been  found  to  predominate,  the  flora 
being  composed  of  the  usual  intestinal  forms.  Aschofr* 
and  Koch  have  demonstrated  in  these  ulcers  the  spirilla 
and  fusiform  bacilli  so  commonly  found  in  the  mouth. 
These  follicular  ulcers  may  be  found  in  any  part  of  the 
intestine,  and  may  be  shallow  erosions,  or  extend  through 
the  follicle  into  the  deeper  tissues.  Hemorrhages  are 
commonly  located  about  the  follicles.  The  epithelial  layer 
is  edematous,  often  showing  an  increased  number  of  cells. 

The  lymph-nodes  may  be  congested,  or  edematous  and 
hemorrhagic.  Pigment  is  usually  present  and  in  some 
cases  the  peripheral  sinus  is  distended  with  pigment- 
loaded  cells.  Where  secondary  infection  has  occurred, 
extensive  necrosis  of  the  glands  is  seen.  This  is  found 
frequently  in  mesenteric  nodes  where  severe  intestinal 
lesions  are  present.  The  nodes  lying  in  the  drainage  paths 
of  hemorrhagic  areas,  especially  the  inguinal  nodes,  show 
active  resorption  of  blood  and  blood  pigments,  and,  as 
noted  above,  may  be  the  seat  of  infection. 

Liver. — In  this  organ,  likewise,  no  change  is  found  with 
sufficient  regularity  to  warrant  its  acceptance  as  a  dis- 
tinctive lesion  of  scurvy.  Fatty  infiltration  is,  however, 
very  common  in  the  centre  as  well  as  in  the  periphery 
of  the  lobules.  It  is  frequently  associated  with  conges- 
tion, which  may  be  so  great  as  to  lead  to  atrophy.  In 
one  case  of  Aschoff  and  Koch  the  picture  resembled  that 
of  primary  liver  atrophy.    The  organ  frequently  contains 


102  SCURVY:    PAST  AND  PRESENT 

extravasated  blood  or  depositions  of  old  blood  pigment. 
It  should  be  noted  that  Boerich  described  early  cirrhosis 
in  several  of  his  cases,  and  that  Aschoif  and  Koch  record 
that  one  of  their  severe,  acute  cases  showed  "a  recent 
cellular  cirrhosis."  An  exceptional  lesion  is  reported 
by  Reinert — a  "leucocytic"  infiltration  of  the  liver  and 
spleen  occurring  in  a  three-year-old  child,  and  resembling 
that  seen  in  pseudoleukemia.  Finally,  it  should  be  re- 
membered in  this  connection  that  Hart  and  Lessing  found 
calcium  deposits  not  only  in  the  muscles  and  adrenal 
glands  of  their  monkeys,  but  also  in  the  liver. 

The  spleen  shares  the  general  congestion  of  the  inter- 
nal organs.  Sato  and  Nambu  invariably  found  large  num- 
bers of  pigment  granules  in  this  organ.  Hirschsprung 
noted  many  Malpighian  corpuscles,  Reinert  describes  a 
true  hyperplasia  of  the  splenic  pulp,  and  others  mention 
infarcts  and  subcapsular  hemorrhages. 

The  kidneys  are  often  normal.  On  the  other  hand, 
various  forms  of  nephritis  are  found,  with  cloudy  swelling 
or  interstitial  change — a  not  infrequent  complication  of 
scurvy.  More  typical  of  the  primary  disease  are  con- 
gestion and  hemorrhages,  the  bleedings  occurring  either 
under  the  capsule,  into  the  interstitial  tissues,  or  into  the 
lumina  of  the  tubules.  Hayem  found  fatty  infiltration 
of  this  organ  and  Aschoif  and  Koch  a  slight  change  of  this 
kind  in  one  case. 

Adrenals. — A  new  interest  in  the  study  of  the  adrenals 
in  diseases  of  the  " deficiency' '  group  has  been  created  by 
the  recent  work  of  McCarrison.  This  author  found  the 
adrenals  increased  in  size  and  weight  in  guinea-pigs  dying 
of  scurvy,  whereas  the  adrenalin  content  of  these  glands 
was  markedly  decreased.  On  section  there  was  hemor- 
rhagic infiltration,  "usually  circumscribed  in  extent  and 


PATHOLOGY  103 

situated  around  the  periphery  of  the  adrenal  cortex." 
This  was  seen  even  in  early  cases  before  hemorrhage  had 
occurred  elsewhere  in  the  body.  He  describes  also  "de- 
generative changes  in  the  cellular  elements  of  cortex  and 
medulla"  consisting  of  vacuolation  and  disintegration  of 
the  cells  with  disappearance  or  loss  of  staining  reactions 
of  their  nuclei.  Rondoni,  some  years  previously,  had 
called  attention  to  this  increase  in  size  and  hyperemia  of 
the  adrenals  in  guinea-pigs  fed  exclusively  cereal  diets. 
He,  as  well  as  McCarrison,  noted  an  increase,  though 
much  less  marked,  as  the  result  of  starvation.  LaMer 
and  Campbell  recently  have  confirmed  McCarrison 's  re- 
port of  an  augmentation  in  the  weight  of  the  adrenal 
glands  in  guinea-pigs  fed  on  diets  deficient  in  the  anti- 
scorbutic factor. 

Comparable  lesions  have  as  yet  not  been  found  in 
human  scurvy.  These  glands  have  been  found  normal  by 
Jacobsthal,  Schoedel  and  Nauwerk,  Ingier  and  Epstein. 
In  the  cases  of  AschofT  and  Koch  no  abnormality  was 
noted  except  an  almost  constant  increase  in  lipoid  content. 
In  those  of  Boerich  the  glands  were  normal  in  all  but  one 
case ;  in  this  instance  the  medulla  was  somewhat  increased 
in  size.  In  passing,  we  may  repeat  that  Hart  and  Lessing 
found  calcium  deposits  in  the  adrenals  of  four  of  their  five 
monkeys,  a  lesion  which  has  never  been  recorded  in  man. 
It  is  valuable  in  this  connection  to  compare  the  adrenal 
in  scurvy  with  that  of  beriberi.  In  this  disorder,  Albeit 
found  the  adrenal  normal  in  one  case,  and  Andrews  de- 
scribes only  congestion  in  his  eighteen  necropsies.  Ono 
found  an  increased  adrenalin  content  in  nine  fatal  cases, 
and  states  that  the  medulla  appeared  "fatter"  than  nor- 
mal. More  data  will  have  to  be  obtained  before  it  can  be 
determined    whether    characteristic    changes    occur    in 


104  SCURVY:    PAST  AND  PRESENT 

scurvy,  and  how  to  interpret  the  hypertrophy  described 
by  several  authors  as  common  to  guinea-pig  scurvy. 

Pancreas. — Sato  and  Nambu  appear  to  be  the  only 
investigators  who  have  described  lesions  in  the  pancreas. 
They  found  hemorrhages  in  one  case  among  thirteen. 

Thymus. — This  organ  has  rarely  been  examined. 
Aschoff  and  Koch  found  no  abnormalities  in  adults,  nor 
did  Jacobsthal  in  a  case  of  infantile  scurvy.  Boerich 
noted  enlargement  in  one  instance. 

Other  Organs  of  Internal  Secretion. — Very  little  attention 
has  been  paid  to  these  organs.  Aschoff  and  Koch  state 
that  the  thyroids  and  hypophyses  were  normal  in 
their  cases. 

Generative  Organs. — No  abnormalities  have  been 
described. 

Central  Nervous  System. — The  most  frequent  abnormal- 
ity of  the  central  nervous  system  is,  as  would  be  expected, 
hemorrhage ;  this  has  been  discussed  in  the  section  dealing 
with  gross  pathology.  No  specific  changes  have  been 
found  in  nerve-cells  or  fibres  of  the  brain. 

In  a  case  of  fatal  scurvy  in  an  infant  a  "focal  de- 
generation of  the  lumbar  cord"  has  been  described, 
extending  for  a  distance  of  about  a  quarter  of  an  inch 
(Hess).  The  lesion  differed  from  that  of  poliomyelitis 
in  the  absence  of  round-celled  infiltration  and  of  the  char- 
acteristic changes  in  the  anterior  horn  cells  (Figs.  3 
and  4).  The  outstanding  feature  was  a  loss  of  cells  in  the 
lateral  groups  of  the  left  anterior  horn ;  there  were  also 
fewer  nerve  fibres  in  this  region,  but  this  diminution  was 
less  striking.  No  definite  interpretation  of  this  case  can 
be  made  as  the  data  are  insufficient  to  permit  a  conclu- 
sion as  to  whether  the  lesion  was  truly  scorbutic  or  the 
result    of   an   associated   process.    Schoedel   and   Nau- 


l> -"■&,.::  •.-..'«: .?.-,  -A'-' 


St**-;*.-* 


** 


% 


■v  ' 


P2 


Fig.   3. — High  power.     Section  of  lumbar  cord  showing  norn.al  cells  in  lateral  group  of  right 

anterior  horn. 


_-     ;  -"'  "\V.\  "f.T.- 


l  ) 


■  •  ■    .. 


-til  ..  v-v  '..'.*■;■  ..-'•■ :'  ^■•^r-'  ••.•■•'•■■■.<■•   :,  Uv       •/•• 


Fig.  4. — High  power.     Section  of  lumbar  cord  showing  focal  degeneration  and  absence  of 

cells  in  lateral  group  of  left  anterior  horn. 


I         ">. — Infantile  -curvy.     Epiphyseal  junction  of  lower  end  of  femur:  (a)  calcined  cartilage  at 

"Truemmerf eld" ;  (b)  hemorrhage  in  the  fibrous  marrow  (Ger  nest-mark).     Bone  cortex  and 

trabeculae  abnormally  thin.     McCallums'  Text  Book  of  Pathology-     VV.  H.  Haunders  ('<>. 


PATHOLOGY  105 

werk  found  no  change  in  the  spinal  cord  stained  by 
Marchi's  method. 

Peripheral  Nerves. — The  sheaths  of  the  large  nerves  as 
well  as  those  of  the  vessels  are  very  often  invaded  by 
hemorrhage.  The  extravasated  blood  is  found  to  lie 
around  but  rarely  among  the  nerve  fibres,  which  do  not 
show  any  pathological  alteration.  Ingier  is  one  of  the 
very  few  to  describe  a  degeneration  of  the  nerve  fibres. 
In  one  guinea-pig  in  which  scurvy  was  induced  she  found 
"many  marked  degenerated  fibrillar  bundles  of  both  sci- 
atic and  peroneal  nerves,  slight  degeneration  of  the 
phrenic  nerves  and  one  vagus  and  its  cardiac  branch.' ' 
Another  animal  is  referred  to  as  having  shown  "very 
marked  and  well-developed  degeneration  of  the  nerves  of 
the  lower  extremities. ' '  It  is  open  to  question  whether 
starvation  played  a  role  in  the  causation  of  these  lesions. 
Schoedel  and  Nauwerk,  and  AschofT  and  Koch  examined 
these  nerves  but  failed  to  find  any  lesions;  the  latter 
directed  their  attention  especially  to  the  vagus  of  twenty- 
two  cases. 

Retinal  hemorrhages  were  found  by  Jacobsthal,  and  by 
Kitamura,  who  records  "decided  edema  of  the  retina, 
marked  bleeding  and  circumscribed  hypertrophy  of  the 
nerve  fibres' '  such  as  is  found  in  albuminuric  retinitis. 
These  changes  are  considered  again  under  the  symptoma- 
tology of  scurvy. 

Bones. — Our  knowledge  of  the  minute  pathology  of 
the  bones  is  far  more  complete  and  detailed  than  that  of 
any  other  structure.  This  was  to  be  expected  in  view  of 
the  fact  that  this  is  the  only  tissue  in  which  the  lesions 
are  diagnostic.  In  considering  the  microscopic  pathology 
it  must  be  remembered  that  all  the  bones  are  rarely 
affected  by  scurvy,  and  that  those  that  are  involved  show 


106  SCURVY:    PAST  AND  PRESENT 

the  scorbutic  changes  to  a  varying  degree.  One  of  the 
peculiarities  of  the  lesion  is  that  it  involves  the  end  of 
the  diaphysis  or  rather  the  junction  of  the  diaphysis  and 
the  cartilage.  The  bones  most  apt  to  show  typical  changes 
are  the  ribs ;  we  shall  therefore  describe  a  section  made 
through  a  costochondral  junction. 

The  costo-chondral  junction  is  generally  swollen,  some- 
what beaded,  and  when  cut  longitudinally  shows  on  gross 
examination  a  transverse  yellowish  bar,  corresponding 
to  the  area  of  disorganization  which  will  be  described 
below.  Under  the  microscope  the  line  of  juncture  is  not 
sharp  and  straight  as  is  normally  the  case,  but  presents 
a  wavy  or  irregular  contour,  the  cartilage  jutting  into  the 
bony  end  of  the  rib,  instead  of  abutting  in  neat  apposition 
to  it.  The  bone  is  hollowed  out  and  irregularly  concave, 
whereas  the  cartilage  presents  a  convex  appearance.  At 
the  site  of  the  junction  is  the  Truemmerfeld  area,  where 
the  normal  tissue  is  splintered  and  fragmented.  Every- 
thing in  a  state  of  disorder — trabecular  of  bone  of  various 
shapes  and  sizes  lie  scattered  about,  the  cells  irregularly 
arranged  and  much  distorted,  signs  of  recent  hemorrhage, 
unrecognizable  detritus.  The  picture  is  that  of  weakened 
bone  having  been  crushed  by  the  pressure  of  the  more  com- 
pact cartilage.  Higher  magnification  shows  that  there 
are  few  osteoblasts  (generally  associated  with  the  deeper 
fragments  of  bone),  a  varying  number  of  intact  red  cells, 
according  to  the  occurrence  of  hemorrhage,  and  occasional 
spindle-  and  star-shaped  connective-tissue  cells.  Cover- 
ing this  mass  of  detritus  there  is  frequently,  as  Aschofr* 
and  Koch  have  emphasized,  more  or  less  protective  fibrin 
which  has  undergone  some  hyaline  or  connective- 
tissue  organization. 

The  cartilage  is  also  not  normal.  Its  cells  do  not  present 


PATHOLOGY  107 

an  orderly  arrangement,  the  proliferating  columns  having 
disappeared  in  the  central  convex  portion,  and  being  pres- 
ent to  a  varying  extent  near  the  periosteal  borders.  If  we 
judge  from  sections  of  early  scurvy  in  guinea-pigs,  this 
disturbance  of  the  columnar  formation  of  the  proliferating 
cartilage  is  one  of  the  early  signs  of  scurvy,  and  is  asso- 
ciated with  an  unevenness  and  irregularity  in  shape  and 
size  of  the  bone  trabecular  In  young  individuals,  where 
cartilage  activity  is  great,  these  changes  are  most 
marked  and  the  entire  zone  of  active  cells  may  be 
somewhat  widened. 

Below  the  Truemmerf eld  is  the  GeruestmarJc  or  frame- 
work marrow,  another  distinguishing  feature  of  scurvy. 
This  extends  for  about  5  to  10  mm.  toward  the  lymphoid 
marrow,  where  it  ends  more  or  less  abruptly.  It  is  com- 
posed of  a  loosely-constructed  fibrillar  tissue  on  a  gelat- 
inous-appearing groundwork,  of  sparsely  scattered  cells, 
and  bony  trabecular  which  are  markedly  thin  and  weak. 
Here  and  there  are  hemorrhages  and  blood  pigment,  espe- 
cially adjacent  to  the  i '  Truemmerf  eld. ' '  Another  feature 
which  strikes  one  at  first  glance  is  that  the  entire  marrow 
area  is  incompletely  filled  by  the  thin  and  greatly-depleted 
trabecular  of  the  spongiosa.  The  question  has  been  raised 
whether  this  rarification  is  to  be  considered  entirely  of 
scorbutic  origin.  It  is  due  evidently  to  a  lack  of  function 
of  the  osteoblasts,  which  are  diminished  in  number,  and 
are  represented  by  a  layer  of  shrivelled  spindle  cells  along 
the  walls  of  the  atrophied  bony  columns.  They  may  fail 
almost  entirely,  as  may  its  osteoid  border,  which  is  signifi- 
cant of  active  bone  tissue.  The  lack  of  bony  structure 
and  rarification  clearly  is  not  due  to  an  increase  in  the 
number  or  the  function  of  the  osteoclasts,  for  these  do  not 
appear  in  excess.    It  is  mainly  the  result  of  normal  bone 


108  SCURVY:    PAST  AND  PRESENT 

resorption  with  a  lack  of  normal  bone  regeneration. 
AschorT  and  Koch  suggest  that  the  frame-work  marrow 
may  be  able  to  manufacture  bone,  but  cannot  accomplish 
this  because  there  is  a  lack  of  material  from  which  to 
make  osteoid  tissue.  This,  they  believe,  constitutes  the 
primary  deficiency — a  lack  or  faulty  development  of 
cement  substance,  which  in  turn  may  depend  on  an  altera- 
tion of  colloid  material.  Regarded  in  this  light,  the  lesions 
of  the  bones  resulting  in  fracture  and  those  of  the  blood- 
vessels resulting  in  rupture  and  hemorrhage  are  depen- 
dent on  a  deficiency  of  the  same  basic  material. 

Hemorrhage  occurs  in  the  bone  as  elsewhere;  it  is 
almost  never  lacking.  It  appears  either  as  large  hemor- 
rhages in  the  spongiosa,  especially  where  the  normal  mar- 
row joins  either  the  G-eruestmark  or  the  Truemmerfeld, 
or  merely  as  scattered  cells,  possibly  the  result  of  diape- 
desis.  The  blood-vessels  in  these  areas  are  narrow  and 
extremely  thin-walled.  The  most  typical  site  of  hemor- 
rhage is  beneath  the  periosteum,  a  lesion  widely  known 
on  account  of  its  clinical  significance  (Fig.  16).  Here  the 
blood  may  extend  for  a  considerable  distance  along  the 
shaft,  but  rarely  beyond  the  epiphyseal  line.  The  clot 
forms  readily,  demonstrating  that  the  nature  of  the  hemor- 
rhage is  not  a  defect  in  coagulation,  and  in  its  midst  may 
be  seen  fibrin,  pigment,  granulation  tissue,  and  more  or 
less  firm  connective  tissue — constituting  the  callus.  The 
inner  surface  of  the  periosteum  is  frequently  lined  with 
newly-formed  bone  and  with  a  more  or  less  dense  deposi- 
tion of  lime  salts,  which  becomes  heavier  in  the  course  of 
the  healing  process,  and  is  readily  observed  in  radio- 
graphs. This  periostitis  ossificans  may  result  in  the  clot 
being  surrounded  by  a  perfect  shell  of  bone,  with  bony 
columns  penetrating  the  deeper  layers. 


• 


Fig.   G. — Posterior-anterior  view  of  shoulder  of  infant    (R.  S.)    17  months 

old.     Severe  scurvy.     Subperiosteal  hemorrhage  of  humerus,  and  separation 

of  upper  epiphysis. 


Fio.  7.    -Anterior-posterior  view  of  Bame   Bhoulder  (see   fig.  6)   22 
months  later.    Complete  restitution  of  epiphysis  without  deformity 

of  humerus. 


PATHOLOGY  109 

As  the  result  of  the  lack  of  bone  formation  and  the 
consequent  weakening  of  the  corticalis  and  the  spongiosa, 
frequently  a  separation  of  the  diaphysis  from  the 
epiphysis  results.  This  lesion  should  not  be  regarded  as  a 
true  separation,  for,  as  Barlow  pointed  out,  the  line  of 
cleavage  is  not  at  the  junction,  but  below  it,  involving-  the 
uppermost  region  of  the  diaphysis.  It  is  therefore  correct 
to  speak  of  a  fracture  or  infraction.  This  lesion  is  gener- 
ally accompanied  by  a  deformity  of  the  surface  contour 
of  the  junction,  due  to  a.  displacement  of  the  cartilage,  as 
a  result  of  which  "angular  beading"  of  the  rib  is  brought 
about.  In  some  instances  the  cartilage  is  "telescoped" 
into  the  crushed  end  of  the  bone.  To  a  varying  extent 
fibrin  covers  the  end  of  the  fractured  bone;  the  angles 
adjacent  to  the  periosteum  contain  blood  which  becomes 
organized  into  dense  connective  tissue,  thus  serving  as  a 
splint  for  the  fractured  parts.  In  the  course  of  healing 
a  large  number  of  foreign  body  giant-cells  appear,  blood- 
vessels sprout  from  the  periosteum  as  well  as  the  bony 
surface,  and  the  necrosed  tissue  gives  place  to  an  active 
formation  of  callus,  which  generally  leads  to  complete 
regeneration  and  restitution.  It  is  remarkable  how  quickly 
and  perfectly  an  epiphysis  may  become  reunited  to  its 
shaft  (Figs.  6  and  7).  Sometimes,  however,  this  takes 
place  with  resulting  deformity,  as  in  the  development  of 
coxa  vara  of  the  femur. 

As  Czerny  and  Keller  have  stated,  it  is  difficult  to 
define  sharply  the  relation  of  bone  fragility  to  scurvy. 
Histologically  there  is  great  similarity  between  the 
"osteotabes  infantum"  described  by  Ziegler  and  condi- 
tions sometimes  found  in  infantile  scurvy.  The  main  dis- 
tinction is  that  in  the  latter  disorder  the  lesion  is  less 
generally  distributed  throughout  the  skeleton,  and  is  par- 


110  SCURVY:    PAST  AND  PRESENT 

ticularly  marked  in  a  limited  area  of  the  bones  (epiphy- 
ses). In  considering  this  question  it  should  be  borne 
in  mind  that,  experimentally,  osteoporosis  and  scurvy  can 
be  brought  about  by  diets  which  are  absolutely  dissimilar. 
For  example,  Bartenstein  showed  that  young  guinea-pigs 
develop  osteoporosis  and  multiple  fractures  on  a  diet  of 
raw  milk  containing  an  adequate  quota  of  antiscor- 
butic vitamine. 

Rickets  and  infantile  scurvy  are  commonly  found  asso- 
ciated, although  they  bear  no  causal  relationship  to  each 
other.  The  distinctive  characteristic  of  rickets  is  the 
broad  area  of  osteoid  tissue  which  is  formed  at  the 
epiphyseal  junction,  a  broad  band  of  incompletely  calcined 
cartilage  not  found  in  scurvy.  In  the  latter  disease  osteo- 
blastic bone  growth  is  greatly  inhibited,  but  what  growth 
does  take  place  occurs  in  a  normal  and  orderly  manner. 
The  osteophytes,  for  example,  which  so  commonly  develop 
at  right  angles  to  the  axis  of  the  bone  in  the  subperiosteal 
hemorrhages,  are  composed  of  apparently  normal  bone. 
Another  marked  distinction  between  the  two  conditions  is 
the  paucity  of  blood-vessels  in  the  cartilaginous  area  and 
in  the  marrow  in  scurvy,  compared  with  the  increased  vas- 
cularity so  generally  encountered  in  rickets.  It  is  evident, 
therefore,  that  although  these  two  nutritional  disorders 
bear  a  superficial  resemblance  to  each  other  pathologi- 
cally, they  are  radically  different  and  almost  antithetical. 


CHAPTER  V 
EXPERIMENTAL  SCURVY 

There  is  no  mention  whatsoever  of  scurvy  in  animals 
previous  to  1895,  when  Theobald  Smith  wrote:  "When 
guinea-pigs  are  fed  with  cereal  (it  has  been  observed  for 
some  years  in  this  laboratory),  with  bran  and  oats  mixed, 
without  any  grass,  clover,  or  succulent  vegetable,  such 
as  cabbage,  a  peculiar  disease,  chiefly  recognizable  by 
subcutaneous  extravasations  of  blood,  carries  them  off  in 
from  four  to  eight  weeks.' '  Smith  did  not  pursue  the 
subject  further. 

Coincident  with  the  appreciation  of  the  value  of 
experimental  methods,  one  would  have  expected  attempts 
to  produce  scurvy  in  animals.  The  disorder  had  been 
recognized  for  a  great  many  years,  the  fact  that  it  was 
occasioned  by  a  dietary  deficient  in  fresh  food  was  widely 
known,  so  that  it  would  seem  natural  for  clinicians  or 
laboratory  workers  to  have  tried  to  induce  the  disease  in 
animals  by  a  similar  restricted  diet.  There  is,  however, 
no  suggestion  of  such  an  experiment  in  the  voluminous 
literature  on  scurvy.  The  explanation  of  the  neglect  of  an 
experimental  study  of  scurvy  appears  to  be  that  this  was 
considered  a  disorder  which  required  little  investigation — 
its  etiology,  its  prevention  and  its  cure  seemed  thoroughly 
understood.  It  is  strange  that  the  mere  fact  that  such  a 
severe  disturbance  responded,  as  if  by  magic,  to  the 
administration  of  simple  foodstuffs  should  not  have 
awakened  curiosity  as  well  as  wonder,  and  stimulated 
inquiry  into  the  nature  and  significance  of  the  cura- 
tive agent. 

in 


112  SCURVY:    PAST  AND  PRESENT 

In  1903  Bolle  published  the  results  of  experiments  on 
guinea-pigs  which  had  been  fed  for  various  periods  on 
raw  or  sterilized  milk.  He  reported  that  the  animals 
developed  a  marked  fragility  of  the  bones,  varying  in 
intensity  in  proportion  to  the  degree  of  heat  to  which  the 
milk  had  been  subjected.  These  changes  Bolle  inter- 
preted as  typical  scurvy,  but  it  is  difficult  to  decide  whether 
the  disorder  was  actually  true  scurvy,  in  view  of  the 
indefinite  description  of  the  bone  lesions. 

Bartenstein  repeated  Bolle 's  work  and  described  in 
detail  the  changes  in  the  bones.  From  his  work  we 
learned  that  it  was  of  little  moment  whether  the  animals 
were  fed  raw  or  sterilized  milk — their  nutrition  failed 
within  about  the  same  length  of  time,  and  they  died 
within  a  month.  The  chief  pathologic  change  was  a 
marked  fragility  of  the  bones,  leading  to  spontaneous 
fractures,  or  to  breaking  of  the  bones  in  the  course  of 
ordinary  manipulation.  Bartenstein  described  the  dis- 
order as  "beginning  with  the  degeneration  of  the  mar- 
row, and  secondarily  leading  to  an  atrophy  of  the  bone 
due  to  increased  absorption  and  deficient  new  formation 
of  bone,  especially  at  the  endochondral  lines  of  ossifica- 
tion. As  the  result  of  the  osteoporosis,  spontaneous  frac- 
tures occur  without  noticeable  hemorrhagic  diathesis." 
He  found  a  deficiency  of  calcium  in  the  bones  of  animals 
suffering  from  even  a  mild  degree  of  this  disorder.  Hart 
and  Lessing  are  of  the  opinion  that  we  cannot  accept 
Bartenstein 's  diagnosis  of  scurvy.  They  compare  this 
disorder  to  that  described  by  Ziegler  as  "osteotabes  in- 
fantum," in  which  there  is  a  more  or  less  pronounced 
"jelly  marrow"  which  has  replaced  the  lymphoid  cells  in 
scattered  areas.  They  sum  up  their  analysis  of  the  ques- 
tion with  the  statement  that ' '  the  primary  marrow  changes 


EXPERIMENTAL  SCURVY  113 

in  the  diaphysis,  the  marked  lacunar  absorption  by  osteo- 
clasts, the  absence  of  subperiosteal  hemorrhages,  do  not 
indicate  typical  scurvy.' '  Schmorl  produced  comparable 
lesions  in  dogs  and  came  to  the  conclusion  that  the  dis- 
order was  one  "very  similar"  to  scurvy  but  not  identical 
with  it,  the  essential  difference  being  that  in  all  animals 
there  was  a  most  marked  absorption  of  bone  by  osteoclasts. 

Similar  results  were  obtained  by  others.  In  1904 
Peiper  and  Eichloff  attempted  to  produce  scurvy  in  dogs 
by  means  of  a  diet  composed  exclusively  of  raw  or  of 
sterilized  milk.  The  following  year  we  find  a  report  by 
Esser  of  feeding  goats  on  sterilized  milk.  None  of  these 
studies  hits  the  mark ;  a  condition  of  f  ragilitas  ossium  was 
produced  rather  than  typical  scurvy. 

In  1907  the  first  systematic  and  convincing  experi- 
mental study  of  scurvy  appeared.  In  this  year  Hoist 
and  Froelich  published  a  preliminary  account  of  their 
classic  work,  undertaken  in  an  endeavor  to  fathom  the 
nature  of  "ship  beriberi,' '  a  disorder  which  disabled  so 
many  of  the  sailors  in  the  Norwegian  navy.  We  must 
remember  that  until  recently  attention  has  been  focussed 
on  the  infectious  diseases,  and  little  thought  given  to  the 
investigation  of  nutritional  disorders.  Although  experi- 
mental investigation  in  this  field  may  be  stated  to  have 
been  initiated  by  this  work,  it  in  turn  had  been  stimulated 
by  a  conception  of  dietary  diseases  which  had  just  begun 
to  be  realized.  This  new  viewpoint  was  the  result  of  the 
work  of  Eijkman.  As  has  been  mentioned  in  considering 
the  pathogenesis  of  human  scurvy,  Eijkman  demon- 
strated that  hens  developed  polyneuritis,  a  disease  resem- 
bling beriberi,  when  fed  on  polished  rice,  and  that  the 
simple  change  to  a  diet  of  unpolished  rice,  or  the  addition 
of  rice  polishings  to  the  dietary,  sufficed  to  protect  or  to 
8 


114  SCURVY:    PAST  AND  PRESENT 

cure.  This  work  had  been  repeated  and  substantiated. 
It  was  evident  to  those  who  considered  the  question  that 
the  old  lines  of  thought  in  regard  to  food  and  dietetics 
inadequately  explained  remarkable  phenomena  of  this 
kind.  It  was  also  clear  that  nutritional  disorders  were 
subject  to  experimental  investigation  in  a  way  similar 
to  the  infectious  diseases,  which  were  absorbing  the  inter- 
est of  the  various  laboratories.  It  is  unnecessary  to  review 
the  rapid  rise  of  investigative  work  in  this  field.  It  may 
be  stated,  in  general,  that  during  the  past  few  years  the 
investigations  of  scurvy  have  become  so  numerous  that 
an  established  research  technic  may  be  said  to  have 
developed  in  connection  with  its  study. 

Attempts  have  been  made  to  produce  scurvy  in  various 
animals,  but  it  has  been  brought  about  regularly  only  in 
the  guinea-pig  and  in  the  monkey.  Experiments  on  the 
dog  are  as  yet  too  few  to  justify  our  regarding  this  animal 
as  definitely  available  for  this  study.  The  nutrition  of 
rats,  mice,  rabbits,  hogs,  pigeons,  fowl,  receiving  a  diet 
identical  with  that  which  regularly  occasions  scurvy  in 
guinea-pigs,  either  progresses  normally  or  a  state  of  mal- 
nutrition develops  which  cannot  be  identified  with  scurvy. 
Recently  Hart,  Steenbock  and  Smith  have  reported  that 
cattle  can  be  reared  to  maturity  on  a  diet  which  will 
produce  scurvy  in  the  guinea-pig  in  four  to  five  weeks. 
We  are  therefore  confronted  with  the  remarkable  and 
inexplicable  phenomenon,  a  fact  concurred  in  by  almost  all 
investigators,  that  a  diet  induces  either  normal  nutrition 
or  malnutrition,  according  to  the  experimental  animal 
employed.  A  diet  of  polished  rice,  or  other  decorticated 
grain,  will  lead  to  the  development  of  scurvy  in  the  guinea- 
pig,  to  polyneuritis  in  the  pigeon  or  fowl,  or,  according 
to  Hoist  and  Froelich,  to  a  combination  of  these  disorders 


EXPERIMENTAL  SCURVY  115 

in  the  hog.1  The  basis  of  these  divergent  results  cannot 
be  surmised,  and  is  worthy  of  the  most  thorough  investi- 
gation. It  may  well  be  that  the  elucidation  of  this  prob- 
lem— for  example,  why  we  are  able  to  bring  about  scurvy 
in  the  guinea-pig  but  not  in  the  rabbit,  will  shed  light  on 
the  pathogenesis  of  this  disorder.  Are  we  to  conclude  that 
some  of  these  animals  have  the  power  to  synthesize  the 
vitamine  whereas  others  must  depend  upon  the  food  for  it, 
or  are  we  to  presuppose  an  ability  to  maintain  normal  life 
and  function  without  any  or  with  a  minimal  amount  of 
this  vitamine?  The  difference  between  these  two  groups, 
the  susceptible  and  non-susceptible  animals,  probably  is 
not  as  absolute  as  we  have  been  wont  to  regard  it.  Re- 
cently Harden  and  Zilva  have  shown  that  although  rats  are 
able  to  thrive  on  a  diet  free  from  antiscorbutic  vitamine, 
they  show  an  appreciable  gain  in  weight  when  this  factor 
is  added  to  the  dietary.  If  such  be  proved  to  be  the  case, 
we  must  regard  the  non-susceptibility  of  the  rat,  the  rab- 
bit, etc.,  as  relative  rather  than  absolute. 

From  time  to  time  a  doubt  has  been  raised  as  to 
whether  we  should  accept  guinea-pig  scurvy  as  the  coun- 
terpart of  human  scurvy.  This  question  can  be  answered 
only  by  comparing  the  disorder  in  the  one  species  with 
that  in  the  other — as  to  mode  of  production,  pathology, 
symptomatology,  means  of  cure  and  all  other  phenomena. 
Viewed  from  these  standpoints  it  is  found  that  in  almost 
every  respect  the  disorder  is  identical  in  man  and  in  the 
guinea-pig.  The  outstanding  distinction  is  the  difference 
in  the  length  of  time  elapsing  before  the  development  of 
symptoms.     In  the  child  or  in  the  adult  it  takes  about 

1Ho^s  fed  on  1.5  kg.  of  rye  bread  and  0.5  kg.  of  meat  heated  to  100° 
or  110°  C.  for  a  half  hour  showed  the  hemorrhages,  loosening  of  the  teeth 
and  affections  of  the  gums  characteristic  of  scurvy,  as  well  as  the  paralysis 
and  neuritis  typical  of  polyneuritis. 


116  SCURVY:    PAST  AND  PRESENT 

six  months  of  the  deficient  diet  before  clinical  symptoms 
are  manifest  and  a  diagnosis  can  be  established;  in  the 
guinea-pig  the  disorder  can  be  recognized  two  weeks  after 
restricting  the  diet.  In  the  one  instance  we  seem  to  be 
dealing  with  a  nutritional  disorder  which  is  chronic  or  at 
least  subacute,  and  in  the  other  with  a  markedly  acnte 
condition.  This  distinction  is  open,  however,  to  certain 
qualifications.  In  the  first  place,  we  must  consider  the 
duration  of  life  of  the  two  species,  the  comparatively  short 
span  of  the  guinea-pig  compared  with  that  of  man.  It 
must  be  borne  in  mind,  furthermore,  that  the  guinea-pig  is 
placed  on  a  diet  absolutely  devoid  of  all  antiscorbutic  vita- 
mine,  whereas  this  rarely  obtains  in  human  beings.  For 
example,  the  diet  which  is  most  markedly  scorbutic  for 
infants  is  the  "malt  soup"  previously  mentioned,  but 
even  this  food  contains  an  amount  of  the  antiscorbutic 
factor  which  is  not  negligible.  But  after  taking  these 
differences  into  consideration,  it  is  nevertheless  evident 
that  the  guinea-pig  is  far  more  sensitive  to  scurvy  than 
man.  This  does  not  indicate  that  the  guinea-pig  is  an  un- 
suitable experimental  animal,  any  more  than  the  fact  that 
the  pigeon  is  more  susceptible  to  polyneuritis  than  man 
indicates  that  it  is  unsuited  to  investigations  of  beriberi. 
It  merely  prevents  our  carrying  out  delicate  quantitative 
experiments,  and  cautions  against  drawing  too  finely- 
spun  deductions.  In  all  nutritional  investigations  it 
should  never  be  forgotten  that  conclusions  drawn  from 
experiments  on  animals  are  merely  provisional,  and  must 
await  substantiation  on  man,  and,  furthermore,  that  where 
differences  in  reaction  are  noted,  the  clinical  data  should 
be  accorded  full  consideration. 

Pathogenesis  of  Guinea-pig  Scurvy. — From  a  pathoge- 
netic point  of  view  guinea-pig  scurvy  and  human  scurvy 


EXPERIMENTAL  SCURVY  117 

show  remarkable  points  in  common.  Any  diet  that  leads 
to  the  development  of  scurvy  in  man  likewise  brings  it 
about  in  the  guinea-pig,  and  contrariwise,  any  food  which 
cures  the  disorder  has  the  same  beneficent  effect  on  both 
species.  This  similarity  extends  so  far  that,  as  will  be 
shown  in  the  chapter  on  antiscorbutics,  the  relative  po- 
tency of  the  various  foods  is  approximately  the  same  for 
man  and  for  the  guinea-pig.  The  parallelism  generally  is 
striking.  The  dietary  which  has  been  commonly  employed 
in  experimental  scurvy  has  been  that  first  suggested  by 
Hoist  and  Froelich,  namely,  oats,  hay  and  water.  Re- 
cently, however,  this  dietary  has  been  enlarged  in  order  to 
make  it  more  complete,  so  as  to  include  adequate  protein, 
water-soluble  and  fat-soluble  vitamine,  and  inorganic 
salts.  To  this  end  the  group  of  workers  at  the  Lister 
Institute  (Chick  and  co-workers,  Harden  and  Zilva)  place 
their  animals  on  a  basal  diet  of  one  part  of  crushed  oats 
and  two  of  wheaten  bran,  and  a  daily  ration  of  50  to  60  c.c. 
of  milk  autoclaved  for  one  hour  at  120°  C.  This  milk 
still  retains  a  small  amount  of  antiscorbutic  vitamine. 
Cohen  and  Mendel  have  employed,  apparently  with  good 
result,  a  "soy  bean  cracker,"  containing  soy  bean  flour 
which  has  been  heated  for  30  minutes  at  15  pounds'  pres- 
sure (120°  C),  3  per  cent,  of  sodium  chloride,  the  same 
percentage  of  calcium  lactate  and  of  dried  brewers '  yeast, 
and  raw  milk  sufficient  to  supply  5  per  cent,  of  butter  fat. 
The  use  of  raw  milk  was  introduced  by  Jackson  and 
Moore,  and  adopted  by  McCollum  and  Pitz  and  again  by 
Pitz  in  a  series  of  interesting  experiments.  The  milk  was 
given  ad  libitum.  The  results  of  these  investigations  were 
puzzling  at  first,  until  it  was  shown  by  Chick,  Hume  and 
Skelton  that  the  dietary  on  which  they  were  based  con- 
tained a  fundamental  error  which  accounted  for  their  lack 


118  SCURVY:    PAST  AND  PRESENT 

of  consistence.  Although  milk  is  not  rich  in  the  antiscor- 
butic factor,  it  possesses  it  in  moderate  degree,  so  that 
the  outcome  will  be  quite  different  according  to  whether  a 
guinea-pig  takes,  for  example,  50  c.c.  or  100  c.c.  daily. 
It  is  quite  evident,  therefore,  that  a  food  of  this  kind  can- 
not be  offered  ad  libitum,  and  that  if  this  rule  is  not  ob- 
served, most  disconcerting  results  will  follow.2  This  basic 
error  in  framing  the  dietary  has  made  it  impossible  to 
accept  the  deductions  of  these  authors.  The  conclusions 
of  McCollum  and  Pitz  are  so  striking  and  have  led  to  such 
wide  discussion,  that  they  require  consideration,  in  spite 
of  the  fact  that  the  error  in  the  dietary  is  now  recognized. 
These  authors  found  that  the  caecum  of  their  animals  was 
greatly  distended  with  putrefying  faeces.  As  the  caecum  is 
extraordinarily  large  and  delicate  in  this  species,  they 
drew  the  deduction  that  the  development  of  scurvy  in 
the  guinea-pig  was  due  principally  to  the  retention  of 
faeces.  "An  impacted  caecum,  the  seat  of  putrefaction, 
may  cause  injury  to  the  caecal  wall,  sufficient  to  permit  the 
invasion  of  the  tissues  by  bacteria,  or  the  animals  may 
perhaps  be  injured  primarily  by  the  absorption  of  toxic 
products  of  bacterial  origin. ' '  Accessory  dietary  factors 
or  vitamines,  according  to  this  theory,  are  supposed  to 
play  no  part  in  the  disorder,  and  antiscorbutics,  such  as 

2  A  guinea-pig  requires  about  80  to  100  c.c.  of  fresh  milk  per  diem  to 
protect  it  from  manifest  scurvy,  if  this  constitutes  its  sole  antiscorbutic 
quota.  There  is,  however,  a  great  difference  in  the  amount  of  milk  which 
individual  animals  consume,  so  that  if  we  furnish  it  ad  libitum  our  results 
will  be  irregular,  one  animal  developing  scurvy  and  another  remaining  well, 
according  to  individual  appetite.  Frequently  guinea-pigs  take  very  little 
rnilk  at  first,  learning  gradually  to  drink  more  and  more,  so  that  it  comes 
to  pass  that  only  after  some  weeks,  if  at  all,  they  take  sufficient  to  afford 
protection.  Under  these  circumstances,  if  any  addition  is  made  to  the 
dietary  after  the  experiment  has  progressed,  the  lack  of  development  or 
cure  of  the  scurvy  may  mistakenly  be  attributed  to  this  newly  introduced 
factor,  whereas,  in  point  of  fact,  it  is  due  to  an  increased  consumption 
of  milk. 


EXPERIMENTAL  SCURVY  119 

orange  juice,  are  considered  to  owe  their  efficacy  mainly 
to  their  laxative  properties,  and  to  be  replaceable  by  other 
laxatives  such  as  phenolphthalein  or  oleum  petrolatum. 
The  efficacy  of  orange  juice  is  supposed  to  be  due  to  its 
content  of  citrates,  and  to  be  replaceable  by  what  was 
termed  "artificial  orange  juice,"  a  mixture  composed  of 
the  various  salts,  citric  acid  and  sucrose,  in  the  propor- 
tions in  which  they  are  found  in  the  natural  juice. 

These  reports  stimulated  renewed  interest  in  experi- 
mental scurvy,  suggesting  new  aspects,  and  therefore 
directing  attention  to  points  requiring  investigation. 
There  were  no  data  at  hand  on  the  consistency  of  the 
contents  of  the  bowel  in  guinea-pigs,  so  that  it  was  neces- 
sary to  make  appropriate  observations  in  normal  and  in 
scorbutic  animals.  It  was  soon  reported  by  various 
workers,  Eappleye,  Cohen  and  Mendel,  Hess  and  Unger, 
and  others,  that  there  was  no  definite  relationship  between 
the  occurrence  of  scurvy  and  impaction  of  the  caecum.  In 
Fig.  8  we  see  portrayed  the  stool  output  of  a  guinea-pig 
during  the  period  in  which  it  was  developing  scurvy,  and 
during  a  subsequent  period  when  it  was  being  cured  by 
means  of  orange  juice.  It  is  clear  that  there  was  no  sig- 
nificant variation  in  the  output  during  these  divergent 
periods.  A  similar  conclusion  was  arrived  at  by  those 
who  examined  the  caecums  of  animals  postmortem.  Cohen 
and  Mendel  write:  "Summarizing  our  experience  with 
nearly  one  hundred  scorbutic  animals,  we  conclude  that 
actual  impaction  of  the  faeces  in  the  caecum  occurred  in 
about  one-quarter  of  the  cases,  and  visible  damage  to  wall, 
i.e.,  congestion  or  hemorrhage,  or  impaction,  or  both,  was 
found  in  perhaps  half  of  the  cases.  It  should  be  noted 
that  this  statement  covers  all  the  diets  we  have  tried.'  * 
We  concur  in  this  conclusion.    Not  infrequently  we  found 


120 


SCURVY:    PAST  AND  PRESENT 


the  cecums  of  markedly  scorbutic  pigs  to  contain  semi- 
fluid faeces,  the  consistency  of  its  contents  depending  on 
the  character  of  the  diet,  quite  apart  from  its  adequacy 
and  lack  of  the  antiscorbutic  factor.  For  example,  a  diet 
rich  in  milk,  containing  100  c.c.  or  more,  led  to  the  for- 
mation of  rather  solid  faeces;  if  oats  were  added  to  the 


Period  I                Period  E                        PeriodUI 

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jcurvy    Gm.  ad  libitum               (1.5 cc.  daily]  added                    discontinued 

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Fig.  8. — Shows  a  period  with  the  development  of  scurvy,  and  one  where  it  was 
cured  by  giving  orange  juice.  It  will  be  noted  that  there  was  no  marked  consti- 
pation while  the  animal  had  scurvy.  During  a  period  of  a  few  days  the  amount 
of  stool  was  scanty,  corresponding  to  the  decreased  intake  of  oats  and  hay  on 
the  days  preceding.    Broken  line  represents  clinical  course  of  scurvy. 

milk  diet  the  faeces  in  the  caecum  were  found  to  be  still  more 
solid,  and  this  portion  of  the  gut  more  often  impacted. 
This  condition  could  be  detected  by  palpation  even  during 
life.  Just  as  we  encountered  scorbutic  animals  on  an  oat, 
hay  and  water  diet,  who  had  semi-fluid  faeces  in  thecaecums, 
so  we  met  with  others  which  were  on  a  milk  diet,  and 
showed  no  signs  of  scurvy,  although  their  caecums  were 
impacted  with  faeces  of  a  putty-like  consistence.    Guinea- 


EXPERIMENTAL  SCURVY  121 

pigs  do  not  seem  to  be  able  to  tolerate  a  diet  containing 
a  large  quantity  of  the  fat  of  cow's  milk.  Such  a  diet  leads 
to  impaction  of  the  large  intestine  resulting  in  death,  but 
does  not  induce  scurvy.  Jackson  and  Moore  produced  a 
condition  of  this  kind  by  feeding  pigs  with  cream  contain- 
ing 26  to  28  per  cent.  fat.  "In  every  case,"  they  write, 
"the  large  intestine  was  distended  with  light  mustard- 
colored  semi-solid  faeces."  This  pathological  condition  is 
not  understood,  but  is  quite  distinct  from  scurvy,  and 
remarkable  in  view  of  the  fact  that  the  milk  of  the  guinea- 
pig  contains  as  high  as  25  per  cent,  of  fat.  It  is  an  inter- 
esting illustration  of  the  marked  biological  difference  in 
the  butter-fat  of  various  species. 

Nor  was  it  found,  as  McCollum  and  Pitz  claimed,  that 
antiscorbutics  were  replaceable  by  laxatives  in  the  diet. 
Without  entering  into  the  details  of  this  aspect  of  the 
subject,  which  will  be  considered  in  the  chapter  on  symp- 
tomatology, it  may  be  stated  that  attempts  to  prevent  the 
occurrence  of  scurvy  or  to  cure  it  by  means  of  laxatives 
invariably  failed.  Chick,  Hume  and  Skelton,  as  well  as 
Hess  and  linger,  gave  oleum  petrolatum  to  a  series  of 
pigs  without  the  slightest  favorable  effect.  Hart,  Steen- 
bock  and-  Smith  recently  reported  that  they  had  adminis- 
tered 1  c.c.  of  this  oil  on  alternate  days  to  one  series  of 
pigs,  and  2  mgm.  of  phenolphthalein  on  alternate  days 
to  another  series,  without  relieving  the  scurvy.  Cohen  and 
Mendel,  in  order  to  test  the  adequacy  of  their  diet  as  to 
roughage,  supplemented  it  with  additions  of  considerable 
filter  paper  and  sawdust,  "without  averting  the  appear- 
ance of  scurvy."  It  is  evident,  therefore,  that  constipa- 
tion does  not  play  an  essential  role  in  the  pathogenesis 
of  scurvy  in  the  guinea-pig,  and  that  antiscorbutics  are 
by  no  means  synonymous  or  interchangeable  with  laxa- 


122  SCURVY:    PAST  AND  PRESENT 

tires.  These  results  accord  with  observations  on  infan- 
tile scurvy. 

The  Pathology. — The  pathology  of  guinea-pig  scurvy  is 
essentially  that  of  human  scurvy.  Hemorrhages  and  sepa- 
rations of  the  epiphyses  or  fractures  of  the  long  bones 
dominate  the  macroscopic  picture.  The  hemorrhages 
are  found  rarely  in  the  gums,  but  are  common  about  the 
joints,  in  the  muscles  of  the  jaw  or  in  those  of  the  hind 
legs.  They  may  be  subcutaneous  and  appear  as  bluish 
discolorations  at  various  parts  of  the  body,  especially  if 
the  disorder  has  resulted  in  death  or  if  infection  has  been 
superadded.  On  stripping  the  skin  we  often  note  hemor- 
rhages in  the  intercostal  muscles,  and  beading  of  the  ribs 
at  the  site  of  the  costochondral  junctions,  least  marked  in 
the  upper  and  in  the  floating  ribs.  This  has  been  fre- 
quently described  in  connection  with  guinea-pig  scurvy; 
its  similarity  to  the  rosary  of  human  rickets  has  been 
drawn  attention  to  recently  by  Jackson  and  Moore.  It 
should  not  be  regarded  as  "pseudo-rhachitic,"  but  as 
typically  scorbutic,  from  a  microscopic  as  well  as  a  macro- 
scopic viewpoint.  On  closer  examination  a  yellowish- 
white  transverse  line  may  be  seen  at  the  epiphyseal 
junction  of  the  ribs,  and  frequently  some  subperiosteal 
hemorrhage.  Beading  of  this  character  has  been  reported 
by  Ingier  also  in  the  "  snuffles  "  of  hogs  and  as  the  result 
of  trauma.  A  similar  enlargement  of  the  chondral  junc- 
tions of  the  sternum  may  be  found  on  examining  its  pos- 
terior surface. 

The  joints  of  the  body  always  show  some  changes.  The 
epiphyses  are  enlarged  to  a  variable  degree,  resembling 
the  epiphyses  typical  of  human  rickets.  As  in  infants, 
this  change  is  met  with  most  commonly  at  the  wrist- joint, 
involving  the  ulna  and  the  radius.    The  knee-joint  is  like- 


EXPERIMENTAL  SCURVY  123 

wise  often  involved,  especially  the  ends  of  the  tibia;  the 
elbow,  ankle,  and  the  shoulder  may  also  show  an  articular 
swelling  of  the  bones.  About  these  joints  hemorrhages 
in  the  subcutaneous  tissues  may  be  seen,  or  edema  extend- 
ing along  the  extremities.  Not  infrequently  a  fracture  of 
one  of  the  long  bones  is  found,  which  may  or  may  not  have 
been  diagnosed  during  life.  The  common  site  of  fracture 
is  the  lower  part  of  the  tibia  or  fibula.  Much  more  fre- 
quent than  fractures  are  separations  of  the  epiphyses, 
which  long  since  have  been  recognized  as  typical  of  infan- 
tile scurvy.  Even  gentle  handling  in  the  course  of  per- 
forming the  necropsy  may  occasion  a  lesion  of  this  kind — 
of  the  tibia  at  the  knee,  of  the  radius  or  ulna  at  the  wrist, 
or  indeed  at  any  of  the  epiphyseal  junctions.  The  in- 
fracted ends  occasionally  may  be  seen  held  insecurely 
by  a  delicate  band  of  periosteum.  The  shafts  of  the  bones 
are  brittle,  rarefied,  and  easily  broken. 

On  opening  the  chest,  slight  hemorrhages  may  be  noted 
in  the  pericardium  and  in  the  visceral  and  costal  pleurae. 
The  heart  is  frequently  enlarged,  and  the  pericardial  sac 
contains  an  excess  of  serum;  the  right  ventricle,  however, 
is  not  found  disproportionately  hypertrophied.  Pneumo- 
nia is  met  with  very  frequently  and  constitutes  a  common 
terminal  infection. 

On  opening  the  abdomen  we  may  note  subperitoneal 
hemorrhages  of  the  muscular  wall  or  of  the  coils  of  intes- 
tine. The  liver  and  spleen  are  generally  normal,  as  is  the 
pancreas.  The  kidney  frequently  shows  minute  hemor- 
rhages beneath  the  capsule  and  on  section. 

The  adrenals  not  infrequently  are  large.  This  fact 
was  first  brought  out  by  Rondoni  and  Montagnani,  and  is 
of  added  interest  in  view  of  its  confirmation  by  McCarri- 
son  as  well  as  by  LaMer  and  Campbell.    Its  significance 


124  SCURVY:    PAST  AND  PRESENT 

is  discussed  at  length  in  the  consideration  of  the  adrenal 
gland  in  human  scurvy.  In  view  of  the  fact  that  fasting 
leads  to  a  similar  hypertrophy,  and  that  guinea-pig  scurvy 
frequently  is  complicated  by  fasting,  these  observations 
should  be  extended.  In  all  investigations  of  this  kind, 
bacterial  cultures  should  be  taken  of  the  adrenals,  or 
other  organs,  to  be  certain  that  there  is  no  complicat- 
ing infection. 

There  have  been  no  reports  as  to  the  effect  of  scurvy 
on  the  size  of  the  testicles,  ovary,  thymus,  thyroid  or 
parathyroid  glands  in  the  guinea-pig,  such  as  have  been 
made  by  McCarrison  in  relation  to  avian  polyneuritis. 

The  alimentary  tract  occasionally  shows  macroscopic 
changes  similar  to  the  lesions  found  in  man.  The  entire 
canal  is  frequently  very  empty,  especially  the  stomach  and 
the  small  intestine,  due  to  the  lack  of  appetite  for  some 
days  previous  to  death.  In  the  stomach  we  may  find 
areas  of  congestion  or  numerous  small  superficial  ulcers 
surrounded  by  congestion  and  covered  with  mucus ;  occa- 
sionally these  ulcers  are  somewhat  larger  and  deeper. 
The  larger  ulcers  are  more  frequently  situated  in  the  first 
part  of  the  duodenum,  often  proximal  to  the  papilla  of 
Vater.  Hoist  and  Froelich  described  this  lesion  in  one  of 
their  early  communications.  More  common  than  ulcera- 
tion of  the  duodenum  is  a  diffuse  congestion  of  its  upper 
part.  This  lesion  is  of  note  because  it  has  been  described 
frequently  in  the  protocols  of  human  necropsies,  and  is 
found  in  beriberi,  in  avian  polyneuritis,  and  in  pellagra 
in  man.  Its  significance  is  unknown,  and  has  indeed  never 
been  discussed. 

Lower  down  in  the  bowel  there  are  occasionally  areas 
of  congestion  and  ulceration,  but  no  section  seems  par- 
ticularly predisposed  to  these  lesions.    The  contents  of  the 


EXPERIMENTAL  SCURVY  125 

bowel,  especially  of  the  caecum,  as  mentioned  above,  de- 
pend more  on  the  character  of  the  food  than  on  the  exist- 
ence of  scurvy.  If  the  diet  has  consisted  of  milk  and  oats, 
the  caecum  will  be  found  full  and  perhaps  impacted, 
whereas  if  hay  and  oats  have  been  fed,  the  caecum  will  be 
less  full  and  its  contents  semisolid. 

In  view  of  the  fact  that  many  of  the  animals  have  taken 
very  little  food  for  some  days  previous  to  their  death,  it 
will  be  well  to  describe  briefly  the  macroscopic  picture  of 
simple  starvation  in  guinea-pigs.  "When  guinea-pigs  are 
given  only  water  they  live  about  one  week ;  if  orange  juice 
is  added  to  this  water-diet  they  succumb  a  little  later  to 
starvation.  Under  all  these  conditions  the  striking  patho- 
logic change — absent  in  scurvy — is  edema.  It  is  true 
that  the  limbs  may  show  slight  edema  in  scurvy,  and  that 
the  pericardial  and  the  pleural  sacs,  and  even  the  perito- 
neal cavity,  occasionally  contain  a  small  quantity  of 
serum,  but  it  is  comparatively  an  insignificant  amount. 
Moreover  it  is  difficult  to  decide  to  what  extent  this  edema 
is  due  to  scurvy,  and  to  what  extent  to  starvation.  In 
typical  starvation,  on  the  other  hand,  such  as  occurs  on 
the  limited  diets  enumerated  above,  we  find  marked 
subcutaneous  edema,  sometimes  a  true  anasarca,  and  fre- 
quently also  ascites.  We  are  reminded  of  the  "war 
edema"  and  its  frequent  association  with  starvation. 
Another  distinction  between  the  two  conditions  is  the  fact 
that  the  marrow  in  starvation  is  yellow  and  not  red  as 
in  scurvy.  In  passing,  it  may  be  mentioned  that  the 
ascites  was  greater  when  orange  juice  had  been  given  than 
where  the  animal  received  only  water. 

In  perusing  the  literature  but  one  study  has  been  noted 
on  the  effect  of  a  scorbutic  diet  on  the  foetus.    This  investi- 


126  SCURVY:    PAST  AND  PRESENT 

gat  ion  was  carried  out  on  a  large  series  of  guinea-pigs  by 
Ingier  (1915).    The  following  comprise  her  conclusions: 

"1.  Pronounced  cases  of  Barlow's  disease  may  be  pro- 
duced in  the  foetus  as  early  as  ten  to  fifteen  days  after 
the  commencement  of  dieting  pregnant  guinea-pigs  with 
oats  and  water.  There  are  wide  individual  variations. 
The  scorbutic  changes  in  the  skeleton  are  greatest  in  the 
earlier  embryonic  stages.  The  foetuses  of  that  period, 
with  practically  no  exceptions,  die  and  show  marked  traces 
of  impeded  growth. 

"2.  Foetuses  from  the  later  period  of  pregnancy  are 
born  alive,  and  apparently  fully  developed,  with  compara- 
tively slight  changes  in  the  osseous  system. 

"3.  Even  a  short  extension  of  the  period  of  extra- 
uterine dieting  on  milk  from  scorbutic  mothers,  and  later 
on  oats  and  water,  is  sufficient  to  change  the  latent  scurvy 
into  a  highly-pronounced  case. 

"4.  The  foetus  cannot  be  kept  alive  longer  than  the 
adult  animal,  about  twenty-eight  days,  either  by  intra- 
uterine dieting  alone  or  by  combined  intra-  and  extra- 
uterine dieting. 

"5.  The  mothers  show  signs  of  the  disease  at  an  early 
period  and  are  more  severely  attacked  than  non-pregnant 
animals.  Death  also  occurs  comparatively  often  in  the 
first  period  of  gestation." 

In  these  experiments  intra-uterine  fractures,  prema- 
ture births  and  still-born  litters  are  frequently  mentioned. 
This  suggests  naturally  an  inquiry  as  to  whether  similar 
occurrences  have  been  observed  in  human  scurvy.  In 
considering  the  pathogenesis  of  human  scurvy,  we  have 
remarked  on  the  meagreness  of  the  data  on  this  most 
interesting  aspect  of  this  disorder.  In  view  of  the  simi- 
larity between  human  and  guinea-pig  scurvy,  we  should 


EXPERIMENTAL  SCURVY  127 

expect  not  only  miscarriages  and  still-births  to  result, 
but  cases  of  congenital  scurvy,  especially  of  the  latent 
or  rudimentary  type. 

Scurvy  Has  Been  Induced  Also  in  the  Monkey. — The  most 
extensive  investigation  of  this  kind  is  that  of  Hart  and 
Lessing,  who  brought  about  scurvy  in  several  young  Ma- 
caci  Rhesi  which  had  been  fed  for  some  months  on  boiled 
condensed  milk  with  the  addition  of  cooked  rice  and  pig- 
nuts. Typical  scurvy  resulted  in  all  but  one  instance,  and 
in  this  case  an  old  animal  was  used  and  a  different  patho- 
logical picture  developed.  These  experiments  require 
brief  reviewing,  as  the  clinical  signs  and  gross  pathology 
in  monkeys  differ  somewhat  from  those  encountered  in 
guinea-pigs,  and  particularly  as  these  distinctions  render 
scurvy  in  monkeys  and  in  infants  practically  identical. 

Apart  from  general  listlessness  and  lack  of  activity, 
the  first  sign  is  hemorrhage  of  the  gums,  the  characteristic 
sign  of  infantile  scurvy.  This  is  stated  to  be  con- 
stant; in  the  guinea-pig  it  is  most  exceptional.  An- 
other sign  characteristic  of  infantile  scurvy  is  the  sub- 
periosteal hemorrhage,  which  in  the  guinea-pig  may  be 
found  as  a  small  effusion  near  one  of  the  larger  joints  or 
the  costochondral  junctions,  but  in  the  monkey  consists 
of  large  effusions,  similar  to  those  described  by  Barlow. 
Subperiosteal  hemorrhages  of  the  cranial  bones  were 
constantly  seen,  and  not  infrequently  involvement  of  the 
scapula  and  of  the  maxilla.  Hemorrhage  into  the  orbit 
leading  to  exophthalmos  and  to  hemorrhagic  discoloration 
of  the  upper  lid — a  lesion  not  infrequent  in  human  scurvy 
— is  also  described;  in  guinea-pigs  we  have  met  with 
exophthalmos  only  in  two  instances.  In  all  other  respects 
scurvy  in  the  monkey  resembles  that  in  the  guinea-pig, 
even  to  the  extent  of  the  scorbutic  rosary  of  the  lower  true 


128  SCURVY:    PAST  AND  PRESENT 

ribs.  Hart  and  Lessing  describe  the  presence  of  the 
"white  line"  of  Fraenkel,  which  is  referred  to  at  length 
in  treating  of  the  symptomatology  of  human  scurvy.  This 
is  a  shadow,  seen  by  means  of  the  X-ray,  traversing  the 
long  bones  near  their  epiphyses — a  definite  "shadow 
band''  associated  with  a  narrow  light  zone  lying  just 
beneath  it.  This  "white  line"  has  been  noted  likewise 
by  Talbot,  Dodd  and  Peterson  in  the  scurvy  of  monkeys. 
Microscopic  Pathology. — Turning  to  the  microscopic 
pathology,  we  find  that  the  changes  are  similar  to  those  de- 
scribed elsewhere  in  connection  with  human  scurvy.  It 
will  be  unnecessary,  therefore,  to  give  more  than  a  genera] 
survey  of  the  typical  alterations.  Little  has  been  added  to 
the  description  of  lesions  so  carefully  depicted  in  the  first 
report  of  Hoist  and  Froelich  (1907).  The  bone  marrow  at 
the  ends  of  the  diaphyses  in  proximity  to  the  epiphyseal 
junction  loses  its  normal  lymphoid  character  and  is  re- 
placed by  a  reticular  or  fibrillated  substance,  the  so-called 
"framework"  marrow  (Geruestmark  of  Schoedel  and 
Nauwerk)  containing  a  homogeneous  mucoid  tissue  and 
only  a  few  osteoblasts  and  marrow  cells.  The  number  of 
blood-vessels  is  considerably  reduced  and  fresh  hemor- 
rhage or  blood  pigment  is  frequently  seen.  The  osseous 
tissue  itself  shows  marked  changes,  corresponding  to  the 
rarification  and  brittleness  noted  on  gross  examination. 
The  osseous  trabecular  are  fewer  in  number  and  those 
which  remain  are  slender  and  irregular,  and  frequently 
appear  as  isolated  islets.  The  cortical  substance  also 
becomes  very  thin.  There  are  marked  alterations  in  the 
intermediate  cartilages,  especially  of  the  ribs.3     Instead 

'  These  changes  are  not  found  in  every  specimen,  so  that  in  order  to  be 
able  to  exclude  scurvy  definitely,  it  is  necessary  to  examine  a  considerable 
number  of  ribs ;  several  may  be  normal,  only  one  or  two  showing  the  char- 
acteristic microscopic  changes. 


EXPERIMENTAL  SCURVY  129 

of  the  cells  being  arranged  in  orderly  rows,  they  are 
irregularly  placed,  and  frequently  greatly  reduced  in  size 
and  number.  The  bone  trabecular  on  which  they  abut  are 
not  well  formed  or  of  equal  length,  and  do  not  present  an 
even  and  transverse  plane,  but  are  misshapen,  small,  so 
that  the  line  of  junction  with  the  cartilage  is  zigzag.  In 
cases  of  marked  scurvy  the  junction  may  be  entirely  dis- 
organized and  deformed,  showing  fractures  of  the  rarefied 
bone  and  hemorrhages  in  the  neighborhood.  This  leads 
frequently  to  a  macroscopic  deformity  of  bone,  a  bulging 
of  the  surface  at  the  costochondral  junction — the  scorbutic 
"beading"  or  "rosary"  of  the  ribs.  Recently  Delf  and 
Tozer  have  described  these  changes,  classifying  them  as 
those  occurring  in  "incipient,"  "definite,"  "acute," 
"chronic  definite,"  and  "chronic  acute"  scurvy.  Fig.  9 
shows  these  types  in  diagrammatic  form.  In  this  fig- 
ure we  see  how  varied  may  be  the  manifestations  of  this 
nutritional  disorder,  according  to  whether  it  has  existed 
for  a  shorter  or  a  longer  time ;  in  some  instances  the  pic- 
ture is  very  puzzling.  The  "incipient  scurvy"  corre- 
sponds to  what  we  have  termed  clinically  "latent  scurvy" 
in  infants,  a  condition  which  cannot  be  diagnosed  and  is 
manifested  merely  by  a  faulty  nutrition  which  responds 
promptly  to  the  addition  of  an  antiscorbutic  to  the  diet. 
There  have  been  no  histologic  examinations  in  man  at  this 
incipient  stage,  but  we  may  infer  that  they  are  similar 
to  the  bony  changes  found  in  the  guinea-pig.  When  the 
scurvy  has  become  chronic  in  an  animal  which  has  lived 
for  months  on  a  quota  of  antiscorbutic  food  sufficient  to 
preserve  life  but  insufficient  to  prevent  the  development 
of  scurvy,  we  find  a  microscopic  picture  at  the  costochon- 
dral junction  differing  widely  from  that  seen  in  the  acute 
stage.  Not  only  are  the  columns  of  cartilage  cells  repre- 
9 


130  SCURVY:    PAST  AND  PRESENT 

sented  merely  by  misshapen  vestiges,  but  an  ossified  band 
(Fig.  95)  is  seen  at  the  junction.  It  is  probable  that  this  is 
frequently  the  cause  of  the  marked  cessation  of  growth 
which  has  been  described  in  connection  with  this  type  of 
scurvy  in  infants.  Delf  and  Tozer  interpret  this  ossified 
band  at  the  junction  as  "an  attempt  to  strengthen  the 
junction  in  an  abnormal  manner,  the  normal  process  hav- 
ing broken  down."  If  the  animal  is  again  deprived  of 
antiscorbutic  food  the  ossified  band  breaks  down,  the 
junction  becomes  deformed  and  disorganized,  and  a 
condition  of  "chronic  scurvy  ( acute )"  is  stated  to 
have  developed. 

It  has  been  noted  by  many  investigators  that  changes 
in  the  teeth  take  place  in  the  course  of  scurvy.  They  be- 
come somewhat  yellow  and  lose  their  glistening  appear- 
ance, and  occasionally  break  off.  The  molars  commonly 
become  loosened,  so  that  they  can  readily  be  removed 
from  their  alveolar  sockets ;  less  frequently  this  is  true  of 
the  incisors.  Until  recently,  however,  this  subject  has  not 
been  studied  in  detail,  and  no  significant  histologic  changes 
in  the  teeth  have  been  described.  Jackson  and  Moore 
showed  that  with  marked  changes  in  the  teeth  there  was 
often  "great  dilatation  of  the  veins  in  the  pulp  attended 
by  more  or  less  hemorrhage  into  the  pulp,"  and  that  "in 
guinea-pigs  fed  on  oats  and  hay  there  was  almost  complete 
necrosis  of  the  pulp  of  the  incisor  teeth,  also  more  or  less 
necrosis  in  the  pulp  of  the  molars." 

Recently  an  intensive  study  of  this  subject  has  been 
made  by  Zilva  and  Wells,  which  is  of  special  interest 
because  it  describes  the  first  beginnings  of  these  lesions, 
and  particularly  because  we  have  no  knowledge  whatsoever 
of  the  dental  changes  which  occur  in  human  scurvy.  These 
investigators  found  a  fibroid  degeneration  of  the  pulp 


EXPERIMENTAL  SCURVY  131 

of  the  teeth,  a  pulpar  fibrosis.  "It  is  clear  at  once,"  they 
write,  "and  it  is  an  important  fact  that  no  trace  of  cellular 
organization,  no  trace  of  cell  nuclei,  no  trace  of  interstitial 
cement  substances  can  be  found  anywhere.  Nerves,  cells, 
blood-vessels,  and  odontoblasts  have  all  shared  the  process 
of  fibrication  and  are  no  longer  recognizable."  These 
radical  changes  in  the  teeth,  brought  about  by  a  deficiency 
of  antiscorbutic  vitamine,  were  demonstrated  not  only  in 
guinea-pigs  but  also  in  monkeys.  In  some  instances  they 
were  found  where  a  histologic  examination  of  the  costo- 
chondral  junctions  showed  nothing  abnormal.  ' '  Profound 
changes  were  recorded  where  the  scorbutic  changes  during 
life  were  so  slight  as  to  be  almost  unrecognizable,"  and, 
they  continue,  "the  mildest  degree  of  scurvy  which  could 
just  be  discovered  at  the  postmortem  examination  pro- 
duced well-defined  changes  in  the  structure  of  the  teeth. ' ' 
If  this  work  is  confirmed,  we  must  consider  the  teeth  as 
one  of  the  first  tissues  of  the  body  to  be  affected  by  scurvy. 
The  authors  quite  rightly  raise  the  question  whether  the 
teeth  of  young  children  may  not  likewise  be  injured  by  a 
deficiency  of  antiscorbutic  vitamine,  whether  this  may 
not  play  a  role  in  the  dental  caries  so  prevalent  among 
civilized  communities.  It  is  evident,  they  state,  that  such 
transient  conditions  of  infantile  scurvy  as  have  been  de- 
scribed by  Hess  as  "subacute"  or  "latent"  scurvy,  may 
occur  more  often  than  is  usually  suspected,  and  may  rea- 
sonably be  expected  to  influence  dentition.  It  seems  quite 
possible  that  the  caries  of  the  permanent  teeth  is  due  not 
only  to  infantile  rickets  but  also  to  infantile  scurvy. 

Besides  the  typical  histologic  changes  in  the  bones 
there  are  alterations  in  other  organs  which  require  men- 
tion. All  investigators  have  found  a  degeneration  of  the 
muscles,  showing  a  loss  of  their  striatums,  swelling  of  the 


132  SCURVY:    PAST  AND  PRESENT 

fibres,  and  the  presence  of  irregularly-distributed  vacuoles 
and  granules.  The  interstitial  tissue  frequently  is  per- 
meated with  edema,  as  we  should  expect  from  gross  ap- 
pearances. Hoist  and  Froelich  have  reported  a  fatty 
degeneration  of  the  heart  muscle,  as  well  as  of  the  epithe- 
lium of  the  mucous  membrane  of  the  glands  of  the  stomach 
and  of  the  intestine.  Hart  and  Lessing,  in  their  protocols 
of  necropsies  on  monkeys,  describe  an  interesting  lesion 
associated  with  the  degenerated  muscle  fibres — a  collec- 
tion of  granules  staining  deep  blue  with  hematoxylin  and 
dissolving  on  the  addition  of  acid.  These  granules,  inter- 
preted as  being  composed  of  calcium,  were  found  in  the 
muscles  of  the  limbs,  of  the  tongue,  and  in  the  heart.  It  is 
reasonable  to  attribute  their  formation  to  an  absorption  of 
bone  throughout  the  body.  Similar  calcium  deposits  were 
seen  frequently  in  the  adrenal  glands,  in  their  cortex,  or 
at  the  border  of  the  cortex  and  medulla.  This  lesion 
gains  special  interest  in  view  of  the  calcium  deposits 
described  so  frequently  in  connection  with  mercurial  poi- 
soning, more  particularly  as  the  symptoms  of  scurvy  and 
of  this  toxic  condition  have  marked  clinical  resemblances. 
There  has  been  but  little  histologic  investigation  of  the 
nerves  in  experimental  scurvy.  In  fact,  the  only  system- 
atic study  of  the  kind  is  that  of  Hoist  and  Froelich, 
whose  attention  was  drawn  to  this  field  in  an  attempt  to 
solve  the  relationship  between  scurvy  and  ship  beriberi. 
These  writers  found  a  true  Wallerian  polyneuritis  in  only 
two  pigs,  one  of  which  had  been  fed  on  wheat  bread  made 
with  yeast,  and  the  other  on  decorticated  barley.  In  many 
instances,  however,  there  was  extensive  degeneration  of 
the  axis  cylinders  without  degeneration  of  the  sheaths. 
They  do  not,  however,  attribute  great  importance  to  these 
changes,  as  the  same  lesions  were  found  in  the  nerves  of 


EXPERIMENTAL  SCURVY  133 

animals  fed  on  cabbage  and  fresh  potatoes.  In  view  of  the 
confusing  reports  on  the  nerves  of  birds  in  experiments  on 
polyneuritis,  one  cannot  be  too  careful  in  drawing  conclu- 
sions from  histologic  studies  of  this  kind. 

In  the  study  by  Jackson  and  Moore  on  experimental 
scurvy  in  guinea-pigs,  the  histology  of  the  blood-vessels  is 
carefully  considered.  "Marked  thinning  of  the  wall" 
was  found  and  depicted ; ' '  the  wall  as  a  whole  had  partially 
melted  away,  leaving  few  traces."  These  parts  of  the 
wall  contained  many  small  round  bodies  resembling  cocci, 
which  were  stained  a  deep  blue  by  the  Wright  and  the 
Giemsa  methods.  These  bodies  were  present  also  in  the 
lumen  of  the  vessel  and  in  the  inner  layers  of  the  more 
normal  portions  of  the  wall.  In  addition  to  such  changes 
in  the  veins,  "lesions  having  the  shape,  location,  and 
characteristics  of  infarcts,  were  found  in  the  ends  of  the 
diaphyses  of  the  long  bones."  As  a  result  of  this  patho- 
logic picture  the  authors  are  of  the  opinion  that  they  may 
have  been  dealing  with  a  mild  infection.  This  is  quite 
possible,  as  scurvy  tends  to  render  the  tissues  less  resist- 
ant to  the  entrance  of  bacteria.  We  believe,  however,  that 
even  if  such  were  the  case,  the  phenomenon  must  be  re- 
garded merely  as  secondary  in  its  relation  to  the  patho- 
genesis of  scurvy. 

Following  the  study  on  the  pathology  of  experimental 
scurvy,  Jackson  and  Moore  undertook  to  determine  pri- 
marily whether  the  small  stained  bodies  seen  in  the 
sections  of  the  scurvy  lesions  were  bacteria.  This  in- 
vestigation has  been  cited  frequently  as  presenting  cogent 
evidence  in  favor  of  the  infectious  nature  of  scurvy,  so 
that  it  will  be  necessary  to  consider  it  fully;  the  general 
question  of  whether  scurvy  is  a  bacterial  infection  is  dis- 
cussed under  the  consideration  of  etiology. 


134  SCURVY:    PAST  AND  PRESENT 

As  is  well  known,  Morpurgo,  a  generation  ago,  claimed 
to  have  produced  rhachitie  lesions  in  young  rats  by  means 
of  artificial  infection  with  a  gram-positive  diplococcns. 
Pappenlieimer  brought  about  similar  lesions  in  rats  by 
the  injection  of  a  suspension  of  bone-marrow  from  a  rha- 
chitie animal.  Koch  injected  a  streptococcus  longus  intra- 
venously into  young  dogs,  occasioning*  gross  bony  changes 
of  the  epiphyses  and  costochondral  junctions,  and 
microscopic  changes  resembling  scurvy— an  irregular  line 
of  ossification  and  "a  framework"  marrow,  which,  how- 
ever, showed  regions  of  osteoid.  Jackson  and  Moody 
were  able  to  isolate  from  the  crushed  tissue  of  their 
guinea-pigs  "a  diplococcus  of  low  virulence  with  a  ten- 
dency to  form  chains  and  produce  green  (color)  on  blood 
agar."  Pure  strains  of  these  organisms  inoculated  into 
the  circulation  of  guinea-pigs  and  rabbits,  living  under 
ordinary  conditions  (a  mixed  diet  consisting  of  green 
vegetables,  hay  and  oats),  gave  rise  in  most  instances  to 
hemorrhagic  and  other  lesions  in  the  bones,  joints,  mus- 
cles, lymph-glands  or  gums.  Hemorrhages  were  found 
beneath  the  periosteum  in  the  region  of  the  lower  incisor 
teeth  and  the  acetabulum  and  ribs.  These  results  are 
far  from  constituting  evidence  in  favor  of  the  microbic 
origin  of  scurvy.  They  show  merely  that  the  tissues  of 
scorbutic  animals  frequently  harbor  bacteria,  and  that 
injections  of  these  bacteria  will  bring  about  hemorrhages 
which  may  be  subperiosteal  in  character.  They  are  open 
to  the  specific  criticism  that  scurvy  was  produced  readily 
in  the  rabbit,  an  animal  which  otherwise  does  not  develop 
scurvy,  and,  furthermore,  they  differ  from  feeding  experi- 
ments in  inciting  scurvy  notwithstanding  the  fact  that 
the  animals  were  receiving  an  antiscorbutic  diet  (green 
vegetables).    Cultures  of  the  hearts'  blood  of  the  affected 


EXPERIMENTAL  SCURVY  135 

animals  were  sterile  in  every  instance;  a  result  obtained 
likewise  by  Hoist  and  Froelich. 

Further  studies  of  this  kind  should  be  carried  out  and 
should  include  cultures  of  the  blood  and  tissues  of  guinea- 
pigs  in  the  various  stages  of  scurvy,  especially  the  early 
stage.  In  addition,  a  histologic  study  should  be  made 
of  the  bones  of  animals  injected  with  bacteria  (preferably 
streptococci),  in  order  to  ascertain  whether  notwithstand- 
ing an  unrestricted  diet,  typical  lesions  can  be  produced 
by  this  means. 

For  further  details  of  the  pathology  of  scurvy,  the 
reader  is  referred  to  the  chapter  on  human  pathology. 

Symptoms.— Let  us  consider  the  symptomatology  of 
guinea-pig  scurvy.  In  the  course  of  an  observation  of 
many  hundreds  of  animals  we  have  been  struck  by  the 
striking  uniformity  of  the  signs  and  symptoms.  The  ani- 
mals made  use  of  were  almost  invariably  of  moderate  size, 
weighing  from  200  to  300  grams.  "Where  heavier  pigs 
were  employed  the  disease  progressed  less  rapidly,  but 
the  signs  were  the  same ;  they  were,  however,  more  diffi- 
cult to  elicit,  owing  to  the  subcutaneous  fat.  Most  of  the 
animals  were  on  a  diet  of  hay,  oats  and  water  ad  libitum, 
but  there  was  no  variation  in  symptoms  where  fat  and 
fat-soluble  vitamine  were  supplied  by  an  addition  of  egg 
yolk  or  of  cod  liver  oil,  or  where  egg  albumen  was  fed  to 
render  the  protein  adequate,  or  where  the  inorganic  salts 
were  supplemented  by  additions  of  sodium  or  cal- 
cium chloride. 

There  is  a  variability  in  the  sign  which  signalizes  the 
onset  of  the  disorder — sometimes  it  consists  of  a  flattening 
of  the  weight  curve,  at  others  of  an  inordinate  excitability 
of  the  animal,  or  frequently  of  a  tender  joint,  generally  a 
wrist.    The  joints  almost  invariably  become  tender  early 


136  SCURVY:    PAST  AND  PRESENT 

in  the  disease,  causing  the  animal  to  wince  and  cry  when  it 
is  examined.  Accompanying  this  tenderness  there  is  often 
slight  swelling  due  to  edema,  or  perhaps  some  hemor- 
rhage, which  alters  the  sharp,  clean-cut  contour  of  the 
joint.  This  edema  may  extend  upward  along  the  tendon 
sheaths.  Soon  the  animal  becomes  lethargic  rather  than 
nervously  active,  and  may  look  ill,  as  manifested  by  a 
roughness  of  its  coat  and  its  unnatural  posture.  Fre- 
quently it  sits  on  three  legs  with  the  tender  hind  leg 
drawn  upward  and  outward  so  as  to  escape  pressure — a 
posture  termed  by  Chick,  Hume  and  Skelton  (1918, 2)  "the 
scurvy  position,"  and  indicative  of  hemorrhage  into  the 
joints  or  muscles.  At  times  it  lies  curled  up,  with  the  side 
of  its  face  resting  on  the  floor,  as  if  to  support  its  painful 
or  sensitive  jaw;  this  they  have  termed  the  "face-ache 
position."  The  two  diagnostic  signs,  however,  are  the 
hemorrhages  about  the  joints  and  the  loosening  of  the 
teeth.  The  diagnosis  frequently  can  be  established  by 
the  twelfth  to  the  fourteenth  day;  the  earliest  diagnosis 
was  made  on  the  eighth  day.  Hemorrhages  appear  some- 
what later  than  tenderness,  and  are  situated  at  the  joints, 
most  frequently  at  the  knee,  which  may  be  markedly 
swollen  and  show  a  bluish  or  reddish  discoloration,  ex- 
tending upward  or  downward  for  some  distance.  Other 
joints  are  often  involved,  frequently  the  wrist,  the  ankle 
or  the  shoulder.  In  other  cases  hemorrhages  into  the 
muscles  are  noted,  especially  of  the  leg  or  of  the  thigh, 
and  later,  especially  toward  the  end,  hemorrhages  from 
the  bowel.  Fractures  or  separations  of  the  epiphyses  may 
be  found  on  examination  or  may  be  occasioned  by  the 
physical  examination.  A  frequent  site  of  this  lesion  is  at 
the  wrist  or  at  the  knee,  involving  the  head  of  the  tibia 


EXPERIMENTAL  SCURVY  137 

or  the  lower  end  of  the  femur.  These  fractures  knit 
rapidly  when  an  antiscorbutic  is  given,  but  result  at  times 
in  deformity. 

Loosening  of  the  teeth  is  another  typical  sign.  It  is, 
however,  one  which  does  not  appear  early  and  is  somewhat 
difficult  to  elicit.  The  molar  teeth  are  generally  involved, 
especially  those  of  the  upper  jaw,  which  may  be  so  com- 
pletely separated  from  their  alveolar  sockets  that  they 
can  readily  be  removed  by  forceps.  It  is,  however,  im- 
possible to  examine  the  molar  teeth  satisfactorily  during 
life.  Far  less  frequently  an  incisor  tooth  becomes  loos- 
ened; more  often  it  loses  its  glistening  appearance  and 
looks  dull  and  yellowish.  Occasionally  an  incisor  tooth 
fractures.  The  gums  are  rarely  altered  sufficiently  to  aid 
diagnosis ;  not  infrequently  they  are  congested  or  bluish, 
rarely  hemorrhagic,  and  never  ulcerous  or  spongy.  This 
is  the  chief  difference  between  the  symptomatology  of 
scurvy  in  the  guinea-pig  and  in  man,  and  probably  is  the 
result  of  lesser  susceptibility  of  the  former  to  infection 
by  pyogenic  bacteria.  In  general,  however,  the  disorder  in 
the  guinea-pig  bears  a  closer  analogy  to  infantile  than  to 
adult  scurvy;  due  to  the  fact,  possibly,  that  young  pigs 
are  generally  used  for  the  experiments. 

A  sign  of  great  interest,  although  not  of  diagnostic  im- 
portance, is  the  "beading"  of  the  ribs  noted  by  many 
observers,  and  emphasized  by  Jackson  and  Moore.  It  has 
been  described  also  in  monkeys  by  Hart  and  Lessing. 
This  is  an  enlargement  or  swelling  of  the  costochondral 
junctions  of  the  ribs,  especially  of  the  lower  true  ribs. 
It  corresponds  clinically  to  the  "beading"  and  the 
"rosary"  so  characteristic  of  infantile  rickets  and  mis- 
takenly termed  the  "rhachitic  rosary."  As  pointed  out, 
in  discussing  the  symptomatology  and  pathology  of  human 


138  SCURVY:    PAST  AND  PRESENT 

scurvy,  this  sign  must  be  regarded  as  truly  scorbutic  in 
animals  as  well  as  in  infants.  The  " rosary' '  is  difficult 
to  palpate  in  pigs  which  have  considerable  subcutaneous 
tissue;  in  thin  animals,  however,  its  course  can  be  fol- 
lowed, the  gradual  development  and  subsequent  disappear- 
ance. In  this  connection  the  enlargement  of  the  epiphyses 
must  be  mentioned,  another  sign  supposed  to  be  character- 
istic of  rickets  in  infants.  Marked  swelling  of  the  wrists 
is  frequently  encountered  in  guinea-pigs  suffering  from 
scurvy — abony  enlargement  involving  the  lower  epiphyses 
of  the  ulna  and  of  the  radius.  This  is  met  with  far  more 
commonly  in  chronic  scurvy  than  in  the  usual  acute  case. 
TVTiere  the  disorder  has  existed  for  a  long  period,  these 
bony  knobs  may  persist  indefinitely,  constituting  the  sole 
residual  sign  of  a  former  scorbutic  condition. 

The  relation  of  loss  of  weight  to  the  development  of 
the  scurvy  requires  consideration.  In  experiments  car- 
ried out  on  rats  to  test  the  diets  in  respect  to  the  water- 
soluble  and  the  fat-soluble  vitamines,  the  weight  curve  is 
used  as  the  main  criterion  to  judge  whether  the  foodstuff 
is  adequate.  In  guinea-pigs  we  cannot  employ  the  weight 
curve  as  a  criterion.  Not  infrequently  an  animal  develops 
scurvy,  and  nevertheless  does  not  lose  in  weight,  but  even 
gains  slowly  and  steadily.  This  occurs  when  the  appetite 
remains  good,  and  the  dietary  is  complete  except  for  anti- 
scorbutic vitamine.  The  same  holds  true  for  human 
scurvy,  as  we  have  noted  in  connection  with  the  symptoma- 
tology. We  have  attempted  to  make  up  for  this  defect  by 
adding  to  the  charts  a  curve  representing  the  clinical 
course  (Pig.  10).  Although  this  curve  is  computed  on  an 
empirical  basis,  it  gives  a  comparatively  true  picture  of 
the  disease  and  is  far  more  exact  than  attempting  to 


EXPERIMENTAL  SCURVY 


139 


portray  the  disease  by  means  of  a  weight  curve.4  Indeed, 
when  we  rely  on  the  latter  method  it  is  impossible  fre- 
quently to  illustrate  graphically  the  reaction  of  guinea- 
pigs  to  various  influences.  Another  disadvantage  of  the 
weight  curve  is  that  it  is  influenced  by  factors  having  no 
direct  relation  to  scurvy,  especially  infections  of  various 
types  which  retard  the  gain. 


Period  I 

_     Hay,  oats;  water 
^  0ni    ,rt  lihiTum 


370 

10     350 

16     330 

12     310 

&     290 


Period  I 

Oran£e  juice 

(l.5cc.  daily)  added 


Period]! 
Orange  juice 
discontinued 


270 
Z50 


^ 

i~\             yu      V 

J      X         ^               £ 

■               V.         v"" 

I        "^ 

,f~.   ""          iX.                                h 

i         i    ~,y    ^t~     -7 

:i  J          w**                     ^         £ 

)              7^Zn     t                                    r      J.  •' 

"7*v     r          ~**\                                                   -W-./ 

>L         — ^'           2 

Fig.  10. — Hay,  oats,  and  water  ad  libitum  during  period  I 
resulted  in  a  lack  of  gain  in  weight,  and  in  a  development  of 
Bcurvy.  During  period  II,  1.5  c.c.  of  orange  juice  were  given 
daily,  and  as  will  be  seen  there  was  a  marked  gain  in  weight 
and  disappearance  of  the  scorbutic  signs,  although,  as  is  gen- 
erally the  case,  they  continue  to  develop  for  a  short  while  after 
an  antiscorbutic  is  given.  When  the  orange  juice  was  discon- 
tinued in  the  third  period,  the  weight  once  more  fell  and  the 
scurvy  redeveloped.  The  broken  line  represents  the  course  of  . 
the  scurvy,  and  is  a  composite  formed  on  the  basis  of  the 
aggregate  of  the  scorbutic  signs.  Each  square  represents  a 
2-day  interval. 

Guinea-pigs  generally  die  of  scurvy  after  having  lost 
about  one-third  of  their  body  weight ;  occasionally  the  loss 
is  greater,  reaching  almost  50  per  cent.  This  loss  is  due 
partly  to  the  scorbutic  condition,  but  to  a  greater  extent 
to  starvation  occasioned  by  a  marked  lack  of  appetite.  In 
this  connection  it  may  be  noted  that  guinea-pigs  fre- 

4  A  maximum  count  of  35  was  formulated,  representing  the  highest 
degree  of  clinical  scurvy.  This  includes  three  grades  of  beading  of  the  ribs, 
four  of  tenderness  of  each  knee  and  wrist  joint,  and  four  of  swelling  of 
each  of  these  joints.  It  is  apparent  from  the  clinical  curve  (Fig.  10)  that 
an  animal  may  have  developed  a  marked  degree  of  scurvy  (20  points),  and 
gained  rather  than  have  lost  in  weight. 


140  SCURVY:    PAST  AND  PRESENT 

quently  lose  for  a  few  days  following  the  addition  of  an 

antiscorbutic  to  the  dietary  (Fig.  11).  This  reaction  is 
evident  from  a  perusal  of  the  weight  charts  of  other  in- 
vestigators, and  occurs  likewise  in  human  scurvy.    This 


Period  I  "Period  H 

Hay,  oqxq,  ad  lib. 

Carrot  water         Plus  dried  milK.lOgm.  daily, 
40ce.  daily  ytom        equivalent  to&Occ    o/ 
35&m  cooked  /rcsh.  fresh  milk. 

youn£  carrots. 


Gm. 
430 

410 

390 

370 

350 

330 

310 

290 

270 

250 

230 

210 

190 

170 

150 


Fig.  11. — These  guinea-pigs  developed  scurvy  in  spite  of 
receiving  a  large  quantity  of  the  water  in  which  young 
carrots  had  been  cooked  for  only  20  minutes.  It  will  be 
noted,  however,  that  although  the  pigs  developed  scurvy 
they  did  not  lose  weight,  as  is  usually  the  case.  After  they 
had  developed  definite  scurvy  they  were  given  in  addition 
the  equivalent  of  80  c.c.  of  a  dried  milk  prepared  by  being 
heated  to  about  116°  C.  for  a  few  seconds.  The  addition 
of  this  milk  to  the  diet  cured  the  scurvy,  showing  that  it 
had  largely  retained  its  antiscorbutic  vitamine. 

loss  is  accompanied,  as  Gerstenberger  has  pointed  out,  by 
diuresis,  which  may  be  so  marked  that  it  is  evident  to  the 
casual  observation  of  those  caring  for  the  animals. 

Exophthalmos  may  be  mentioned  again  in  this  connec- 
tion as  a  very  rare  sign  of  guinea-pig  scurvy.     Haima- 


"         T-     =P       =V 

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EXPERIMENTAL  SCURVY  141 

turia  also  occurs  at  times ;  it  is  not  known  how  frequently 
it  is  present,  whether  it  is  an  early  manifestation  in  the 
guinea-pig  as  in  the  infant,  or  whether  the  source  of  the 
blood  is  the  kidney  or  the  bladder. 

The  superficial  lymphatic  glands  are  frequently  pal- 
pable in  scurvy,  especially  those  in  the  inguinal  region. 
This  sign  is  emphasized  by  some  pathologists.  It  has 
seemed  to  us  attributable  less  to  the  nutritional  condition 
than  to  the  infections  which  so  frequently  complicate 
the  disorder. 

According  to  Jackson  and  Moore  a  rise  of  temperature 
does  not  accompany  scurvy  in  the  guinea-pig.  As  the 
result  of  an  examination  of  nine  guinea-pigs  they  con- 
clude that  "experimental  scurvy  is  a  non-febrile  disease 
in  the  majority  of  affected  animals. ' '  Nor  did  they  find  a 
leucocytosis,  the  average  leucocyte  count  of  eight  scor- 
butic pigs  being  about  8000. 

As  the  data  are  meagre,  a  consideration  of  the  chemical 
alterations  associated  with  the  scurvy  of  guinea-pigs  and 
monkeys  will  be  taken  up  in  conjunction  with  the  metabo- 
lism of  human  scurvy.  The  therapy  of  animal  scurvy 
will  also  be  deferred  (chapter  VI),  as  the  reaction  to 
dietetic  measures  is  practically  the  same  in  man  and  in 
animals.  In  concluding  this  chapter  we  would  call  atten- 
tion to  the  following  interesting  statement  contained  in  the 
recent  paper  by  Delf  and  Tozer:  "In  other  experiments, 
however,  where  a  liberal  supply  of  an  antiscorbutic  was 
given  and  where  the  fat-soluble  A  growth  factor  was 
known  to  be  deficient,  the  resulting  histological  changes  in 
the  rib-junctions  of  the  animals  examined  were  found  to 
resemble  closely  those  of  *  Definite '  or  of  '  Definite 
Chronic '  scurvy.  In  these  test  cases  the  antiscorbutic 
chosen  was,  we  believed,  deficient  in  the  fat-soluble  A 


142  SCURVY:    PAST  AND  PRESENT 

growth  factor  (for  example,  orange  juice).  This  fact 
is  mentioned  because  in  the  case  of  an  animal  not  receiv- 
ing an  adequate  supply  of  fat-soluble  A  the  resulting 
changes  in  the  junctions  are  not  dissimilar  from,  and  are 
likely  to  be  confused  with,  those  caused  by  scurvy  alone.' ' 
If  this  observation  is  confirmed,  it  emphasizes  the  neces- 
sity in  nutritional  experiments,  of  constructing  a  dietary 
which  is  complete  in  every  respect  except  the  one  under 
investigation;  it  also  suggests  the  development  of  new 
pathologic  entities  in  relation  to  other  nutritional  dis- 
orders resulting  from  a  lack  of  the  accessory  food  factors. 


CHAPTER  VI 
ANTISCORBUTIC  FOODS 

Historical  Review.1 — It  is  impossible  to  state  when  and 
how  the  knowledge  of  the  value  of  antiscorbutic  foodstuffs 
came  to  be  appreciated.  It  is  probable  that  the  potency 
of  herbs  and  fruits  in  scurvy  was  known  empirically  to 
individuals  and  groups  of  people  long  before  the  fact 
gained  general  recognition.  A  most  interesting  history  of 
antiscorbutics  is  given  in  the  excellent  work  of  Hirsch  and 
in  our  great  classic  on  scurvy  by  Lind.  The  first  realiza- 
tion of  the  value  of  lemons  and  oranges  seems  to  have 
been  the  result  of  a  chance  discovery.  Budd  tells  us  that 
in  the  sixteenth  century  sailors  of  a  Dutch  sailing  vessel 
laden  with  these  fruits  were  attacked  with  scurvy,  and 
that,  when  they  partook  of  the  lemons  and  oranges  in  the 
cargo,  a  miraculous  cure  resulted.  He  narrates  also  the 
following  striking  incident,  which  is  mentioned  likewise 
by  Lind : 

In  the  year  1600  four  sailing  vessels  left  England 
for  the  East  Indies.  The  sailors  on  three  of  these  ships 
did  not  receive  lime  juice,  whereas  those  on  the  fourth 
received  their  daily  quota.  The  men  of  the  first  three 
ships  suffered  severely  from  scurvy,  but  those  on  the 
fourth  escaped. 

1  It  is  of  interest  that  John  Hall,  the  son-in-law  of  Shakespeare,  and 
a  prominent  physician  of  Warwickshire,  was  one  of  the  first  to  urge  the 
use  of  antiscorbutics.  In  a  quaint  work  entitled,  "  Select  Observations  on 
English  Bodies,  or  Cures  both  Empericall  and  Historical"  (1657  London), 
he  describes  how  he  cured  scurvy  by  means  of  brewing  a  beer  or  ate 
from  "  Scorbutick  hearts,  viz. :  scurvy  grass,  water-cresses  and  brook  lime." 
This  book,  wbich  ran  through  at  least  two  editions,  has  not  achieved  the 
popularity  of  the  works  of  the  father-in-law. 

143 


144  SCURVY:    PAST  AND  PRESENT 

In  an  excellent  work  on  ' '  Scorvey, ' '  published  in  1685, 
Harvey  wrote :  "TVheref  ore  most  acids,  especially  spirit  of 
salt  marine,  juice  of  sorrel,  Unions,  citrons,  etc.,  are  so 
deservedly  extolled  in  some  scorbutic  distempers  and 
seconded  with  good  success."  Thus  we  see  that  even  at 
this  early  date  it  was  taken  for  granted  that  citrous  fruits 
possessed  virtue  in  curing  scurvy.  Bachstrom  (Obser- 
vations circa  Scorbutum,  1734)  evidently  was  well- 
acquainted  with  the  antiscorbutic  value  of  scurvy  grass, 
and  relates  the  story  of  a  sailor  severely  disabled  from 
scurvy  who  was  put  ashore  to  perish  on  Greenland,  and 
crawled  on  the  ground,  grazed  on  scurvy  grass  like  a  beast 
of  the  field,  and  was  able  to  return  home  perfectly  recov- 
ered.   (Cited  from  Lind.) 

The  credit  for  forcing  a  general  acceptance  of  the 
antiscorbutic  value  of  fresh  food  belongs  to  Lind.  He 
did  not,  however,  have  an  easy  task,  and  in  1747,  in  order 
to  convince  those  who  still  were  skeptical,  he  resorted  to 
an  experiment  on  human  beings.  Twelve  patients  in  his 
hospital  were  given  the  same  diet,  except  that  some  re- 
ceived sea-water  in  addition  to  their  dietary,  others  vine- 
gar, or  elixir  of  sulphuric  acid,  or  a  daily  portion  of  cider, 
or  oranges  and  one  lemon  daily.  The  last  two  groups, 
as  we  should  expect,  recovered  quickly;  one  man  who 
received  cider  improved,  but  in  no  other  case  was  any 
alleviation  noted. 

Lind  extols  the  value  of  lemons  and  oranges,  of  ber- 
ries, of  sour  cabbage,  of  cider,  and  of  all  fresh  fruits  and 
vegetables.  In  spite  of  the  fact,  however,  that  Lind's 
teaching  was  based  on  an  experience  with  thousands  of 
patients  suffering  from  scurvy  in  the  naval  hospital,  his 
ideas  did  not  take  root.  It  required  an  event  which  came 
directly  under  the  official  eye  to  bring  about  radical 


ANTISCORBUTIC  FOODS  145 

changes  in  the  diet  of  the  sailors.  In  1795  the  English 
Fleet  suffered  from  a  severe  epidemic  of  scurvy,  which 
was  finally  controlled  by  giving  the  sailors  fresh  vege- 
tables and  fruit.  This  therapeutic  result  was  so  con- 
vincing that  thenceforth  a  daily  ration  of  lime  juice  was 
ordered  for  the  sailors  and  a  regular  issue  provided  for 
the  navy.  This  marks  the  cessation  of  scurvy  as  a  scourge 
of  the  British  navy.  From  this  time  the  disease  appeared 
only  sporadically.  The  sharp  decrease  in  the  incidence 
can  be  appreciated  by  Budd's  statement  that  1457  cases 
of  scurvy  were  admitted  to  the  Royal  Naval  Hospital  in 
1780,  whereas  in  1810  an  English  physician  reported  that 
in  the  seven  preceding  years  he  had  not  treated  a  single 
patient  in  this  hospital  suffering  from  scurvy.  In  an- 
other marine  hospital,  between  the  years  1806  and  1810, 
only  two  cases  of  scurvy  were  admitted. 

Nothing  was  done  for  the  British  merchant  service 
until  over  half  a  century  later,  although  scurvy  continued 
to  make  its  appearance  among  the  sailors  with  varying 
severity.  Smith  states  in  (the  article  on  this  subject 
in  Allbutt's  System  of  Medicine:  "In  1864  it  was 
pointed  out  by  Doctor  Barnes  that  during  the  twelve 
years  following  1851,  1058  cases  of  scurvy  had  been  ad- 
mitted into  the  hospital  ship  Dreadnought."  In  1854  a 
law  was  passed  requiring  every  vessel  to  carry  an  ade- 
quate supply  of  lime  juice.  This  law,  however,  failed  in 
effect,  due  to  the  fact  that  a  large  part  of  the  lime  juice 
was  adulterated.  A  new  shipping-act  was  passed,  there- 
fore, in  1867,  with  the  object  of  preventing  adulterations, 
at  the  same  time  increasing  the  daily  quota  for  each  sea- 
man from  half  an  ounce  to  one  ounce. 

It  may  be  of  interest  to  add  a  few  words  concerning 
certain  antiscorbutics  which  have  been  under  discussion 

10 


146  SCURVY:    PAST  AND  PRESENT 

or  recognized  for  so  many  years  that  they  have  acquired 
an  historical  aspect.  One  of  these  foodstuffs  is  sauer- 
kraut, which  was  recognized  by  Lind  in  1772  as  having 
particular  potency  in  this  disease.  It  is  interesting  to  note, 
in  this  connection,  that  this  writer  appreciated  the  close 
relationship  of  acidity  to  antiscorbutic  virtue.  "One 
quality, ' '  he  writes,  ' i  entering  the  most  perfect  antiscor- 
butic composition  is  a  vegetable  accescency. ' '  He  prized 
sauerkraut  for  its  inherent  value,  and  particularly,  be- 
cause he  found  that  "sour  cabbage  will  keep  for  an  East- 
India  voyage. ' ' 

The  famous  navigator  Cook,  whose  voyages  were  re- 
markable for  the  freedom  from  illness  which  his  sailors 
enjoyed  and  the  absence  of  scurvy,  always  kept  a  large 
supply  of  sauerkraut  on  hand.  It  was  believed  by  many 
that  the  immunity  of  the  Dutch  seamen  to  scurvy  was  due 
to  their  large  consumption  of  this  vegetable.  As  the 
result  of  this  empirical  knowledge,  the  English  navy 
in  1780  introduced  the  use  of  sauerkraut  into  its  ration. 
As  just  noted,  however,  this  antiscorbutic  was  supplanted 
some  few  years  later  by  an  issue  of  lime  juice. 

It  is  common  knowledge  that  outbreaks  of  scurvy 
follow  closely  upon  a  failure  of  the  potato  crop.  This  has 
been  particularly  the  case  in  Ireland,  where  it  was  espe- 
cially evident  in  relation  to  the  great  epidemic  of  scurvy 
in  1847.  Hoist  and  Proelich  inform  us  that  "all  scurvy 
epidemics  in  Norway  in  the  nineteenth  and  beginning  of 
this  century  followed  failure  of  the  potato  crop."  Nor 
is  this  danger  past.  In  an  article  entitled  "The  Role  of 
Antiscorbutics  in  Our  Dietary,' '  the  author  recently  re- 
ported that  the  partial  failure  of  the  potato  crop  in  the 
eastern  part  of  the  United  States  led  to  the  development 
of  scurvy  in  numerous  institutions,  in  one  of  which  over 


ANTISCORBUTIC  FOODS  147 

200  cases  of  definite  scurvy  developed  in  the  spring  (1916). 

The  occurrence  of  scurvy  in  the  navy  and  on  sailing 
vessels  has  been  associated  in  the  minds  of  many  with  the 
large  amounts  of  salted  meat  which  necessarily  was  in- 
cluded in  the  dietary.  It  was  evident  that  meat  that  was 
salted  had  no  antiscorbutic  value,  but  the  query  has  been 
raised  whether  eating  a  considerable  amount  of  salted 
meat  did  not  induce  scurvy.  Lind  mentions  "  flesh  long 
salted"  as  leading  to  the  development  of  scurvy.  The 
question  of  the  value  of  meat  as  an  antiscorbutic  is  of 
importance  at  the  present  time,  chiefly  in  connection  with 
Polar  expeditions  and  army  rations.  As  the  result  of  an 
outbreak  of  scurvy  in  the  Polar  expedition  of  1875-6, 
a  British  Arctic  Survey  Committee  was  appointed  to 
make  an  investigation.  In  1877  it  reported  that  "al- 
though the  scurvy  was  due  to  the  absence  of  lime  juice 
from  the  sledge  dietaries,  meat  in  large  amounts  is  able 
to  prevent  the  disease."  Stefansson  also  emphasized  the 
value  of  meat  in  preventing  scurvy  in  the  Polar  regions. 
In  his  expeditions  he  has  found  that  raw  meat,  if  taken 
in  sufficient  quantity,  is  able  to  afford  complete  protection. 
Jackson,  who  lived  for  some  years  among  the  Samoyeds, 
tells  us  that  this  tribe,  owing  to  the  fact  that  they  con- 
sumed considerable  reindeer  meat,  never  suffered  from 
scurvy  in  spite  of  the  fact  that  they  ate  no  vegetables  or 
fresh  fruit  during  the  winter. 

The  following  account,  a  personal  communication 
from  Dr.  Harrison  J.  Hunt,  who  spent  four  years  in 
the  Arctic  regions,  is  of  interest  in  this  connection : 

"For  some  four  years  I  was  with  the  Smith  Sound 
Eskimos,  on  the  northwest  coast  of  Greenland.  These 
people  get  nothing  but  animal  food  normally,  and  have 
lived  that  way  for  many  generations,  yet  are  healthy,  of 


148  SCURVY:    PAST  AND  PRESENT 

good  physique,  and  are  normal  in  other  ways.  Scurvy 
was  unknown  to  them  as  far  as  I  could  ascertain;  cer- 
tainly there  was  none  while  I  was  among  them.  Much 
of  their  meat  is  eaten  raw,  and  the  rest  only  partly  cooked ; 
that  is,  '  rare  done. ' 

"Whalers  who  were  accustomed  to  winter  in  Hudson 
Bay  practically  always  had  scurvy  in  the  crew.  It  was 
common  knowledge  among  the  captains  that  fresh  meat 
was  curative  of  scurvy,  and  it  was  their  practice  to  obtain 
meat  from  the  Eskimos  whenever  possible  for  that  pur- 
pose. The  last  English  expeditions  to  the  South  Polar 
regions  were  afflicted  with  scurvy  which  was  entirely  and 
quickly  eradicated  by  the  use  of  fresh  seal  meat  in  the 
place  of  salt  meats  and  canned  foods.  They  do  not  state 
that  this  meat  was  eaten  raw  or  even  rare  cooked.  On 
the  Danish  coast  of  Greenland,  during  seasons  poor  in 
game,  scurvy  is  quite  common,  but  the  natives  there  live 
largely  on  breadstuffs  (very  coarse  rye  bread).  Person- 
ally, during  my  four  years  in  the  Arctic,  I  took  no  fresh 
vegetables  whatever,  or  other  commonly-called  antiscor- 
butics, relying  solely  on  rare  or  raw  meat.  I  never  was 
stronger  or  more  healthy  in  my  life.  I  did  have  dried 
fruits  and  vegetables,  and  usually  plenty  of  fresh  bread. 
Usually  the  Eskimos  eat  their  raw  meat  in  a  frozen  con- 
dition, and  I  can  attest  that  it  is  extremely  palatable  in 
that  condition.,, 

We  do  not  wish  to  discuss,  in  this  place,  the  value  of 
meat  as  an  antiscorbutic;  in  passing,  however,  it  may  be 
said  that,  as  in  the  case  of  the  other  antiscorbutics,  its  effi- 
cacy will  depend  largely  upon  the  amount  consumed.  The 
British  Mesopotamia  Commission  Report  of  1917  shows 
that  scurvy  can  develop  on  a  ration  which  includes  28 
ounces  of  meat  a  week.    We  must  remember,  however,  that 


ANTISCORBUTIC  FOODS  149 

this  refers  to  cooked  meat,  whereas  in  the  Polar  expedi- 
tions meat  generally  was  eaten  in  a  raw  state. 

Recently  an  historical  inquiry  has  appeared  in  an 
article  by  Chick,  Hume  and  Skelton  as  to  the  antiscorbutic 
virtue  of  limes  and  lemons.  This  sketch  is  of  exceptional 
interest  because  it  treats  of  the  oldest  and  most  cherished 
antiscorbutics,  and  particularly  because  it  has  unearthed 
a  peculiar  fallacy  in  their  connection.  As  they  state,  there 
would  appear  to  be  every  reason  for  believing  ' i  that  the 
use  of  so-called  lime  juice  was  responsible  for  the  disap- 
pearance of  scurvy  from  the  British  navy  in  the  first 
decade  of  the  nineteenth  century."  It  would  seem,  how- 
ever, that  the  lime  juice  which  gained  this  great  reputa- 
tion in  the  navy  some  125  years  ago  was  in  reality  lemon 
juice,  and  that  it  was  not  until  about  50  years  ago  that 
lime  juice  was  really  used.  These  authors  show — by  one 
of  those  striking  human  experiments  which,  occasionally, 
is  available — that  in  a  Polar  exploration  which  was  organ- 
ized in  1850  lemon  juice  was  issued  to  each  man,  and  that 
no  case  of  scurvy  developed,  whereas  in  a  similar  expe- 
dition which  went  out  in  1875  lime  juice  was  issued  and 
scurvy  developed  the  following  spring  with  great  severity 
among  the  sledge  crews.  This  investigation,  therefore, 
seems  to  prove  that  lime  juice,  the  prototype  of  antiscor- 
butics, has  been  accorded  a  false  position ;  that  in  reality 
the  sailors  of  the  past  have  been  protected  by  lemon  juice. 

Antiscorbutic  Foods. — As  far  as  has  been  ascertained, 
the  antiscorbutic  food  factor  exists  in  all  fresh  vegetable 
and  animal  tissues,  being  present  to  a  far  greater  degree 
in  the  former  than  in  the  latter.  It  is  distinguished  by 
being  associated  in  nature  with  cells  which  are  the  seat  of 
active  metabolism,  just  as  the  water-soluble  vit amine  is 
associated  mainly  with  cells  which  are  in  an  inactive 


150  SCURVY:    PAST  AND  PRESENT 

or  dormant  state.  Vegetables  or  fruits  may  be  mildly  or 
highly  antiscorbutic;  there  is  indeed  a  remarkable  differ- 
ence in  their  content  of  antiscorbutic  factor  or  vitamine. 
They  vary  widely  also  in  the  degree  to  which  their  potency 
is  affected  by  physical  or  chemical  conditions.  In  this 
chapter  the  most  common  animal  and  vegetable  antiscor- 
butic foodstuffs  will  be  considered  and  the  effect  which 
processes  such  as  drying,  canning,  change  of  reaction,  etc., 
exert  on  their  specific  value.  Their  therapeutic  applica- 
tion in  the  prevention  and  cure  of  scurvy  will  be  consid- 
ered in  a  subsequent  chapter.  Until  recently  our  knowl- 
edge of  this  subject  was  empirical  and  inaccurate;  as  the 
result  of  scientific  work,  however,  carried  out  during  the 
past  few  years  in  different  parts  of  the  world,  quantitative 
and  comparative  figures  of  antiscorbutic  food  values  have 
been  evolved. 

Milk. — It  is  important  to  have  as  accurate  an  idea  as 
possible  of  the  value  of  milk  as  an  antiscorbutic,  as  the 
infant  depends  on  it  during  the  first  months  of  its  life  for 
a  supply  of  this  essential  factor.  Considerable  attention 
has  been  paid  to  this  question  in  the  last  few  years,  and 
recent  reports  tend  to  confirm  the  former  estimations 
which  had  been  overlooked  and  forgotten.  In  1847  Curran 
wrote  that  in  the  Irish  epidemic  of  this  year  they  had 
admitted  to  the  Dublin  Union  Hospital  80  cases  of  scurvy 
which  had  been  on  a  diet  which  included  one  pint  of  milk 
daily,  but  was  deficient  in  vegetables.  From  this  experi- 
ence he  realized  that  milk  was  not  rich  in  the  principles 
which  protect  against  scurvy.  In  the  following  year 
Parkes  came  to  the  same  conclusion,  stating  that  500  to 
750  c.c.  of  raw  milk  did  not  always  suffice  to  prevent 
scurvy.  In  addition  to  these  opinions  concerning  adults, 
similar  conclusions  have  been  drawn  from  clinical  experi- 


ANTISCORBUTIC  FOODS  151 

ence  with  infants.  Barlow  (1894)  realized  that  a  small 
amount  of  milk  was  insufficient  to  protect  against  scurvy. 
Still  writes:  "The  antiscorbutic  power  of  fresh,  unboiled 
milk  is  evidently  slight."  In  1914  Hess  and  Fish  pointed 
out  that  "milk  must  not  be  considered  as  having  potent 
antiscorbutic  properties."  Nevertheless,  when  this  ques- 
tion was  raised  recently  by  the  experimental  work  of 
Jackson  and  Moore,  and  that  of  McCollum  and  Pitz,  it 
was  not  appreciated  that,  like  other  antiscorbutics,  milk 
must  be  regarded  from  a  quantitative  standpoint,  and 
that,  as  it  is  a  weak  antiscorbutic,  its  effect  must  depend 
largely  on  the  quantity  consumed. 

The  first  laboratory  work  on  this  subject  was  that  of 
Froelich  in  1912,  who  showed  that  guinea-pigs  could  be 
protected  by  an  exclusive  diet  of  fresh  milk,  and  that  raw 
milk  is  more  effective  than  heated  milk.  In  his  work,  the 
amount  of  milk  taken  by  the  animals  was  not  measured,  so 
that  it  is  impossible  to  glean  from  it  more  than  these  gen- 
eral conclusions.  In  the  following  year,  as  a  result  of  some 
quantitative  experiments,  Funk  stated  that  he  was  able 
to  protect  guinea-pigs  with  50  c.c.  of  fresh  milk  in  addition 
to  an  oat  diet.  This  estimate,  as  subsequent  workers 
showed,  is  too  low.  Chick,  Hume  and  Skelton  were  the 
first,  however,  to  investigate  the  antiscorbutic  potency  of 
milk  in  a  systematic  and  convincing  manner.  They 
demonstrated  that  if  the  daily  consumption  of  fresh  milk 
was  less  than  50  c.c,  a  guinea-pig  died  almost  as  quickly 
as  if  it  received  no  milk;  if  the  daily  quota  varied  from 
50  to  100  c.c,  a  greater  or  less  protection  from  scurvy 
was  observed,  varying  proportionately  with  the  amount 
consumed;  if  100  to  150  c.c.  were  taken  daily,  which  practi- 
cally amounts  to  a  complete  milk  diet,  satisfactory  growth 
and  development  occurred,  and  no  symptoms  of  scurvy 


152  SCURVY:    PAST  AND  PRESENT 

were  observed.  This  represents  in  a  general  way  the 
present  conception  of  the  antiscorbutic  power  of  milk. 
In  passing,  it  may  be  remarked  that  it  is  not  altogether 
clear  why  50  c.c.  of  milk  do  not  afford  partial  protection, 
and  prolong  the  life  of  the  animal  for  a  definite  length 
of  time.  The  authors  conclude  that  "milk  is  evidently 
a  food  poor  in  the  antiscurvy  accessory  factor,  and  a 
ration  large  in  comparison  with  that  of  other  antiscor- 
butic materials  is  necessary  to  afford  satisfactory  pro- 
tection from  scurvy. "  The  error  must  be  avoided,  how- 
ever, of  regarding  milk  as  a  standard  article  of  diet  con- 
taining a  definite  and  specific  amount  of  vitamine  per 
cubic  centimetre.  It  will  be  shown  later  that  this  point 
of  view  cannot  be  taken  in  regard  to  vegetables,  and  it  is 
probable  that  it  cannot  be  assumed  for  milk. 

A  general  conception  of  the  antiscorbutic  potency  of 
cow's  milk  may  be  gleaned  from  the  fact  that  it  requires 
a  minimum  of  about  sixteen  ounces  (500  c.c.)  daily  to 
protect  an  infant  from  scurvy  or  to  cure  it.  Twelve 
ounces  have  failed  to  effect  a  cure  in  several  instances, 
although  the  milk  was  raw  and  of  the  best  grade.  If 
it  is  pasteurized,  a  larger  quantity  is  required,  depend- 
ing upon  various  conditions  connected  with  the  heating 
process  and  upon  the  age  of  the  milk,  circumstances 
fully  discussed  in  relation  to  etiology.  Thus  it  becomes 
evident  that  pasteurized  milk  assumes  a  twofold  role,  act- 
ing as  an  antiscorbutic  if  little  of  its  vitamine  content 
has  been  destroyed  and  if  a  large  quantity  is  consumed, 
or  leading  to  the  development  of  scurvy  when  one  or 
both  of  these  conditions  is  unfavorable.  The  same 
holds  true  for  milk  which  has  been  boiled  for  a  short 
period.     If  the  milk  has  been  heated  twice,  it  tends  to 


ANTISCORBUTIC  FOODS  153 

produce  scurvy ;  if  it  is  condensed,  the  greater  part  of  its 
antiscorbutic  value  is  destroyed. 

It  seems  necessary  to  emphasize  again  the  important 
fact  that  dried  milk  may  possess  marked  antiscorbutic 
potency,  depending  on  the  method  of  preparation  (Fig. 
11).  As  stated,  sixteen  ounces  of  milk  dried  by  the  Just- 
Hatmaker  process  cured  scurvy  promptly,  in  spite  of  the 
fact  that  the  milk  had  been  dried  six  months  previously. 
Here,  therefore,  is  a  food  of  high  caloric  value,  compact, 
antiscorbutic,  and  stable.  The  fact  that  milk,  in  spite  of 
drying,  retains  this  labile  vitamine  for  so  long  a  period, 
demonstrates  that  it  is  available  in  the  most  remote  parts 
of  the  world,  and  that  the  possibilities  of  its  transporta- 
tion are  unlimited. 

Little  is  known  regarding  the  antiscorbutic  content  of 
the  milk  of  the  various  domestic  animals.  Some  claim 
that  goat's  milk  is  notably  rich  in  this  particular,  but 
experiments  with  it  are  too  few  to  warrant  conclusions. 
Lind  writes:  " Goats,  of  all  animals,  afford  the  richest 
whey,  possessed  of  the  greatest  antiscorbutic  virtue  .  .  . 
which  in  a  singular  manner  restores  the  constitution  when 
weakened  and  impaired  by  scurvy."  Human  milk  pos- 
sesses about  the  same  potency  as  cow's  milk,  as  men- 
tioned in  the  discussion  of  the  occurrence  of  infantile 
scurvy  in  countries  where  the  adult  form  is  endemic. 
Twelve  ounces  of  human  milk,  from  a  woman  on  a  liberal 
and  varied  diet,  barely  sufficed  to  alleviate  the  symptoms 
of  a  case  of  moderate  intensity. 

FEUIT  JUICES 

Orange  and  Lemon  Juice. — The  most  thoroughly  stud- 
ied antiscorbutic  foods  are  orange  and  lemon  juice,  which 
have  been  singled  out  because  they  contain  the  anti- 


154  SCURVY:    PAST  AND  PRESENT 

scorbutic  factor  in  the  highest  concentration.  It  has 
been  ascertained  through  the  work  of  various  investiga- 
tors that  guinea-pigs  require  about  3  c.c.  daily  of  either 
of  these  juices  to  protect  them  from  scurvy,  but  that 
about  half  this  amount  is  sufficient  to  prevent  the  mani- 
festation of  clinical  signs. 

Both  of  these  juices  withstand  heat  remarkably  well. 
Orange  juice  can  be  boiled  for  10  minutes  without  noting 
any  diminution  of  its  antiscorbutic  value,  and  lemon  juice 
heated  to  110°  C.  without  appreciably  losing  its  efficacy. 
However,  orange  juice  undergoes  some  change  as  the 
result  of  being  heated  in  an  autoclave  for  45  minutes  at  a 
temperature  of  110°  under  10  to  15  pounds  pressure. 
Although  6  c.c.  of  this  heated  preparation  were  able  to 
prevent  the  development  of  scurvy,  the  guinea-pigs  did 
not  gain  nearly  as  well  as  those  which  received  3  c.c.  of 
the  unheated  juice.  It  seemed  as  if  there  was  a  destruc- 
tion of  some  factor  apart  from  the  antiscorbutic  principle. 

In  spite  of  the  fact  that  these  juices  withstand  heat 
well,  they  are  sensitive  to  some  other  conditions.  Orange 
juice  which  had  been  stored  in  the  cold  for  three  months 
was  unable  to  protect  guinea-pigs  in  the  dosage  of  3  c.c. 
per  animal,  resembling  in  its  action  the  autoclaved  juice. 
When  this  orange  juice  was  six  months  old,  double  this 
quantity  failed  to  protect;  throughout  this  period  it  was 
kept  in  the  ice-box  and  covered  with  a  layer  of  oleum 
petrolatum  to  avoid  the  access  of  air  or  possible  contami- 
nation. Harden  and  Zilva  met  with  a  similar  experience, 
and  state  that ' '  after  storing  treated  (concentrated)  lemon 
juice  for  about  a  fortnight  in  a  cold  room,  a  marked  loss 
can  be  observed  in  its  potency.' ' 

These  authors  reported  also  that  when  orange  juice  is 
rendered  slightly  alkaline  it  loses  its  antiscorbutic  po- 


ANTISCORBUTIC  FOODS  155 

tency.  This  question  was  investigated  in  relation  to 
canned  tomato  juice,  as  well  as  to  orange  juice,  and  it  was 
found  that  shortly  after  having  been  rendered  0.05  N 
alkaline  to  phenolphthalein,  neither  of  these  foods  had 
lost  an  appreciable  amount  of  its  antiscorbutic  factor. 
Five  cubic  centimetres  per  capita  daily  of  freshly-alka- 
lized orange  juice  were  able  to  cure  a  group  of  pigs  which 
had  developed  scurvy  on  another  diet.  If,  however,  24 
hours  were  allowed  to  elapse  instead  of  only  one-half 
to  one  hour,  between  the  alkalization  and  the  feeding,  then 
a  considerable  amount  of  the  antiscorbutic  factor  was  lost. 
The  same  general  rule  seems  to  hold  for  alkalization  as 
for  heating,  i.e.,  the  length  of  time  the  antiscorbutic  food 
is  subjected  to  the  deleterious  influence  is  fully  as  im- 
portant as  the  intensity  of  the  process.  Advantage  has 
been  taken  of  the  fact  that  freshly-alkalized  orange  juice 
retains  its  potency,  in  using  it  intravenously  in  the  treat- 
ment of  infantile  scurvy. 

Subcutaneous  injections  of  neutralized  orange  juice 
failed  to  cure  scurvy  in  guinea-pigs;  Harden  and  Zilva 
were  equally  unsuccessful  with  large  doses  of  their  con- 
centrated lemon  juice.  This  is  of  interest  in  view  of  the 
marked  therapeutic  result  which  Shiga  obtained  with  sub- 
cutaneous injections  of  the  water-soluble  vitamine  in 
pigeons  suffering  from  polyneuritis.  It  should  be  added 
that  Hoist  and  Froelich  (1912)  failed  to  cure  scurvy 
in  guinea-pigs  by  intraperitoneal  inoculations  of 
orange  juice. 

Lemon  juice  or  orange  juice  may  be  dried  and  lose 
little  of  its  antiscorbutic  power.  In  their  paper  of  1912 
Hoist  and  Froelich  reported  the  efficacy  of  lemon  juice 
evaporated  in  a  vacuum,  and  recently  Harden  and  Zilva 
published  experiments  which  proved  that  "by  evaporat- 


156  SCURVY:    PAST  AND  PRESENT 

ing  the  treated  lemon  juice  to  dryness  in  an  acid  medium 
an  active  dry  residue  is  obtained."  Still  more  recently 
Givens  has  shown  that  orange  juice  reduced  to  a  pow- 
dered form  by  means  of  a  spraying  process  has  lost  little 
of  the  antiscorbutic  factor.  These  results  prove  that 
under  certain  conditions  the  antiscorbutic  factor  with- 
stands drying;  one  of  these  favorable  influences  is  an  acid 
reaction,  and  another,  rapidity  of  desiccation.2 

Lime  Juice. — Recently  an  investigation  of  lime  juice 
has  been  carried  out  by  Chick,  Hume  and  Skelton.  They 
were  "unable  to  detect  any  significant  protection  in  a 
daily  ration  of  from  5  to  10  c.c. ' '  of  preserved  lime  juice 
which  was  several  months  or  a  year  or  more  old." 
Crude  lime  juice  of  various  ages  had  slight  antiscorbutic 
value,  affording  only  partial  protection  in  a  daily  ration 
of  5  c.c.  Even  fresh  juice  was  found  not  to  be  very  effi- 
cacious compared  with  lemon  juice.  The  authors  conclude 
that  "the  relative  value  of  these  two  fruit  juices  deduced 
from  the  trials  with  monkeys  is  therefore  in  accord  with 
that  obtained  in  the  experiments  with  guinea-pigs,  i.e.,  the 
value  of  fresh  lemon  juice  is  approximately  four  times 
that  of  fresh  lime  juice. "  Hoist  and  Froelich  in  1907 
carried  out  a  similar  but  less  extensive  investigation. 
They  also  found  that  lime  juice  was  unable  to  protect 
guinea-pigs  from  scurvy.  Fuerst,  a  co-worker  of  Hoist, 
continued  this  work,  and  in  his  article  of  1912  stated  that 
guinea-pigs  should  not  be  protected  by  a  daily  addition  to 
their  ration  of  25  g.  of  lime  juice;  these  guinea-pigs  re- 
ceived a  mixed  diet  consisting  of  dry  vegetables,  butter, 
almonds  and  malt  extract.     These  two  reports  of  the  Nor- 

a  Preserved  mulberries  which  had.  been  sugared  and  cooked  for  one- 
quarter  to  one-half  an  hour  were  found  by  Hoist  and  Froelich  (1912)  to 
possess  good  antiscorbutic  power  three  months  later. 


ANTISCORBUTIC  FOODS 


157 


wegian  investigators  on  this  interesting  subject  should 
have  attracted  attention. 

Other  Fruits. — A  word  may  be  said  in  regard  to  some 
other  fruits.  The  antiscorbutic  potency  of  raspberries 
was  tested  by  Hoist  and  Froelich  (1912)  and  found  com- 
parable to  oranges  and  to  lemons.     The  juice  was  also 


TABLE  3 

Table  Showing  the  Relative  Distribution  of  the  Antiscorbutic  Factor 
in  the  Commoner  Foodstuffs* 


Classes  of  Foodstuffs 


Antiscorbutic 
Factor 


Classes  of  Foodstuffs 


Antiscorbutic 
Factor 


Meat,  Fish,  Etc.: 

Lean  meat  (beef,  mut 
ton,  etc.) 

Liver 

Tinned  meats 

Beef  juice 

Milk,  Cheese,  Etc.: 

Milk,  cow's,  whole  raw 

Milk,  cow's,  skim  raw 

Milk,  cow's,  dried . .  . 

Milk,  cow's,  boiled . . 

Milk,  cow's,  pasteur- 
ized  

Milk,  cow's,  condensed 

(sweetened) 

Eggs: 

Fresh 

Dried 

Cereals,  Pulses,  Etc.: 

Wheat,  maize,  rice, 
whole  grain 

Wheat  germ 

Wheat,  maize,  bran .  . 

White  wheaten  flour, 
pure  corn  flour,  pol- 
ished rice,  etc 

Linseed,  millet 

Dried  peas,  lentils,  etc. 

Soy  beans,  haricot 
beans 

Germinated  pulses  or 
cereals 


+ 
+ 
0 

+ 

+ 

+ 

Less  than  -+- 

Less  than  + 

Less  than  -f 

?0 
?0 


0 
0 
0 

0 

++ 


Vegetables  and  Fruits: 

Cabbage,  fresh 

Cabbage,  cooked 

Cabbage,  dried 

Swede,  raw  expressed 
juice 

Lettuce 

Carrots,  fresh  raw .... 

Carrots,  dried 

Beetroot,  raw,  ex- 
pressed juice 

Potatoes,  raw 

Potatoes,  cooked 

Potatoes,  dried 

Beans,  fresh,  raw 

Onions 

Lemon  juice,  fresh 

Lemon  juice,  preserved 

Lime  juice,  fresh 

Lime  juice,  preserved 

Orange  juice 

Raspberries 

Grapes 

Apples 

Bananas 

Tomatoes  (canned) .  . . 

Miscellaneous: 

Yeast,  autolyzed 

Meat  extract 

Beer 

Cod  liver  oil 

Olive  oil 

Human  blood 


+  +  + 

+ 

Very  slight 

+  + 
+  + 

+ 

0 

Less  than  -f 

'  +  ' 

0 

+  + 

+  + 
+  +  + 

+  + 

+  + 

Veiy  slight 

+  +  + 

+  + 

+ 

Very  slight 

+  + 


0 
0 
0 
0 
0 

+ 


*Thi»  table  is  a  modification  of  one  prepared  by  the  Medical  Research  Committee 


158  SCURVY:    PAST  AND  PRESENT 

highly  resistant  to  heat,  so  that  10  c.c.  of  freshly-pressed 
juice  were  of  protective  value,  even  after  it  had  been  sub- 
jected to  100  or  110°  C.  for  one  hour.  Guinea-pigs  which 
were  thus  treated  showed  no  microscopic  signs  of  scurvy 
in  any  of  the  ribs,  in  the  tibiae  or  the  femora. 

These  authors  also  reported  that  they  found  banana 
and  apple  poor  in  antiscorbutic  power,  30  g.  daily  being 
insufficient  to  protect  a  guinea-pig  (Table  3).  This  was 
our  experience  with  banana  in  the  treatment  of  infants 
suffering  from  mild  scurvy.  The  banana  has  been  shown 
by  Sugiura  and  Benedict  to  be  poor  also  in  the  water- 
soluble  vitamine.  It  would  be  of  interest  to  determine 
the  difference  in  vitamine  content  between  the  fully-ripe 
and  the  unripe  fruit. 

In  view  of  the  fact  that  grapes  are  used  considerably 
in  the  treatment  of  infantile  scurvy,  it  is  of  importance 
to  realize  that  they  are  poor  in  the  antiscorbutic  principle. 
Chick  and  Rhodes  found  that  three  of  four  guinea-pigs 
receiving  20  g.  daily  developed  scurvy;  they  rated  the 
potency  as  ten  times  less  than  that  of  orange  juice. 

VEGETABLES 

It  is  everyday  knowledge  that  fresh  vegetables 
are  of  great  value  in  the  protection  from,  and  cure  of, 
scurvy.  The  first  experimental  investigation  of  this 
subject  was  that  of  Hoist  and  Froelich,  published  in 
1907,  and  continued  in  a  series  of  papers  extending  to 
1916.  These  investigators  tested  the  potency  of  a  large 
number  of  vegetables  by  feeding  them  in  varying  quanti- 
ties to  guinea-pigs.  They  found  that  all  vegetables  have 
antiscorbutic  value  but  to  a  markedly  varying  degree. 
Cabbage,  sorrel  leaves,  endive,  head  salad,  and  dandelion 
leaves,were  found  to  be  of  most  avail  in  protecting  against 


ANTISCORBUTIC  FOODS  159 

scurvy,  whereas  carrots,  cooked  potatoes  and  cooked  tur- 
nips, and  cauliflower  proved  to  be  of  less  value.  In  gen- 
eral, it  may  be  stated  that  the  leafy  vegetables  have  more 
antiscorbutic  power  than  the  roots  or  the  tubers.  This  jf 
generalization,  we  shall  see,  is  not  without  exception,  e.g., 
the  swede.  Similar  experimental  work  has  been  recently 
carried  on  by  a  group  of  investigators  at  the  Lister  In- 
stitute, who  have  added  considerably  to  our  knowledge 
in  this  field.  In  all  this  experimental  work  cabbage  has 
been  found  to  be  the  most  potent  of  the  vegetables,  and 
therefore  experiments  have  centered  about  it  just  as  in 
considering  fruits  the  work  has  centered  about  orange 
juice  or  lemon  juice.  We  shall,  therefore,  discuss  in  detail 
its  reaction  to  heat  and  dehydration. 

Cabbage. — Hoist  and  Froelich  found  that  1  g.  daily 
of  fresh  cabbage  afforded  nearly  complete  protection  to 
guinea-pigs,  and  Delf  has  corroborated  this  work.  This 
amount  is  sufficient  to  prevent  the  development  of  mani- 
fest scurvy,  although  it  does  not  induce  satisfactory 
growth.  In  this  respect  it  is  comparable  to  giving  1.5  c.c. 
of  orange  juice  daily.  If  guinea-pigs  take  only  0.5  g.  of 
raw  cabbage,  scurvy  will  develop ;  whereas  2  g.  or  more 
will  promote  satisfactory  growth  and  no  scorbutic  changes 
will  be  found  on  microscopic  examination. 

Effect  of  Heating. — Vegetables  are  of  decidedly  less 
antiscorbutic  value  when  cooked  than  raw;  cabbage,  for 
instance,  on  being  boiled  is  weakened  about  one-half. 
Heating  to  110°  C.  for  an  hour  destroys  almost  all  of  its 
antiscorbutic  factor.  Delf 's  tests  did  not  show  so  great 
a  loss.  She  came  to  the  conclusion,  of  theoretical  and 
practical  value,  that  slow  cooking  at  a  low  temperature 
is  much  more  deleterious  than  rapid  cooking  at  a  higher 
temperature.     Hess  and  Unger  found  that  carrots  lost 


I 


160  SCURVY:    PAST  AND  PRESENT 

much  of  their  antiscorbutic  power  after  boiling,  and  that 
this  was  the  result  of  a  true  destruction,  the  vitamine  not 
having  been  merely  dissolved  in  the  water  of  boiling;  for 
if  guinea-pigs  consumed  40  c.c.  per  capita  of  this  water, 
they  were  not  protected  against  scurvy  (Fig.  11).  Acidu- 
lating the  water  with  10  per  cent,  vinegar  did  not  reduce 
the  loss,  an  experience  similar  to  that  of  others  using 
citric  acid  or  lemon  juice. 

Vegetables  cannot  be  considered  from  an  antiscorbutic 
standpoint  as  a  standard  and  uniform  foodstuff,  as  they 
vary  in  their  content  of  this  factor  according  to  their 
freshness  and  age.  This  was  demonstrated  by  means  of 
feeding  experiments  with  carrots.  For  example,  35  g.  of 
old  carrots,  such  as  were  used  for  feeding  the  laboratory 
animals,  afforded  but  little  protection  after  having  been 
cooked  in  an  open  vessel  for  about  45  minutes,  whereas  the 
same  amount  of  young  carrots  cooked  this  way  protected 
the  guinea-pigs.  It  is  obvious  that  this  distinction  is  of 
importance  in  evaluating  the  antiscorbutic  content  of  the 
various  foods,  and  in  considering  whether  individuals  and 
groups  of  individuals  are  receiving  an  adequate  quota 
of  antiscorbutic  vitamine.  It  will  be  noted  later  that  it 
is  also  of  importance  in  connection  with  the  potency  of 
dehydrated  vegetables.  Recent  experiments  indicate  that 
not  only  age,  but  the  degree  of  ripeness  must  be  con- 
sidered in  appraising  the  food  value  of  vegetables.  Feed- 
ing experiments  showed  that  tomatoes  which  were  fully 
ripe  were  more  potent  than  those  which  were  slightly 
green.  Probably  many  other  factors  play  n  role  in  de- 
termining the  richness  of  vegetables  in  vitamine.  It  may 
not  be  immaterial  whether  they  are  allowed  to  ripen  on 
the  vine  or  shrub,  or  mature  subsequently.  The  nature 
of  the  soil  may  also  affect  the  antiscorbutic  quality  of 


ANTISCORBUTIC  FOODS  161 

the  vegetables  or  fruit.  So  that  it  is  evident  that  we  must 
not  be  schematic  in  considering  this  question,  and  must 
realize  that  a  table  of  antiscorbutic  values,  such  as  accom- 
panies this  text  (Table  3),  does  not  furnish  definite  and 
inflexible  values. 

There  is  a  marked  difference  between  vegetables  and 
vegetable  juices  in  keeping  quality,  and  in  their  reaction 
to  heat  and  to  acid.  In  general,  it  may  be  stated  that 
the  juices  are  much  more  sensitive.  Hoist  and  Froelich 
brought  out  this  point  in  1912  and  enlarged  upon  it  in 
their  publication  of  1916.  The  different  juices  vary 
greatly  in  this  respect;  for  example,  dandelion  juice  is 
acutely  sensitive  to  heat,  whereas  sorrel  leaves  withstand 
high  temperatures  very  well.  In  regard  to  these  differ- 
ences an  analogy  may  be  drawn  to  the,  fruit  juices. 
Lemon,  orange  and  raspberry  juices  are  markedly 
thermo-stable,  but  lime  juice  is  weakened  markedly  by 
heat.  Many  of  these  juices  are  protected  by  the  addition 
of  acid — 5  per  cent,  of  lemon  juice  increasing  the  thermo- 
stability of  cabbage  juice — whereas,  as  we  have  stated, 
little  is  gained  by  cooking  vegetables  in  an  acid  medium. 

Potato. — The  civilized  world  is  dependent  for  its  quota 
of  antiscorbutic  foodstuff  largely  upon  the  potato.  It 
might  be  thought,  therefore,  that  this  would  signify  that 
the  potato  is  endowed  with  great  antiscorbutic  power. 
Such  is  not  the  case,  however,  as  demonstrated  both  by 
laboratory  tests  and  clinical  experience.  Considering  its 
importance,  there  have  been  surprisingly  few  feeding  ex- 
periments carried  out  with  potato.  Hoist  and  Froelich 
(1912)  found  that  17  g.  of  potatoes,  steamed  at  100°  C. 
for  30  minutes,  afforded  but  slight  protection,  and  that  it 
required  20  g.  to  fully  protect  a  guinea-pig.  Givens  and 
Cohen  failed  to  ward  off  scurvy  by  means  of  cooked  pota- 
11 


162  SCURVY:    PAST  AND  PRESENT 

toes  fed  to  the  equivalent  of  5  g.  of  the  raw  vegetable 
(guinea-pigs  will  not  eat  raw  potatoes).  There  are  no 
accurate  figures  as  to  the  quantity  of  potatoes  needed  to 
protect  a  human  being  from  scurvy.  The  statement  of 
Doctor  Guy,  however,  who  after  careful  study  of  convicts ' 
diets,  concluded  that  14  ounces  daily  would  protect  them 
from  scurvy  (if  the  ration  included  one  ounce  of  other 
fresh  vegetable  and  4  ounces  of  meat),  is  probably  close 
to  the  mark.3  With  the  experience  that  potatoes  play 
such  a  significant  role  in  the  prevention  of  scurvy,  how 
are  we  to  interpret  the  fact  that  they  are  only  mildly  anti- 
scorbutic ?  Potatoes  are  consumed  in  very  large  amounts ; 
in  the  Temperate  Zone  probably  twice  as  many  pounds 
of  potatoes  are  consumed  during  the  winter  as  of  all  other 
vegetables  combined  (Fig.  1).  It  is  evident,  therefore, 
that  in  a  practical  evaluation  of  antiscorbutic  foodstuffs, 
not  only  the  intrinsic  antiscorbutic  potency  must  be  con- 
sidered, but  also  the  quantity  of  the  vegetable  or 
fruit  consumed. 

Swede. — We  cannot  leave  the  consideration  of  vege- 
table antiscorbutics  without  adding  a  few  words  as  to  the 
value  of  swede  juice,4  which  has  been  recently  highly 
recommended  by  Chick  and  Rhodes,  who  found  it  com- 
parable to  the  cabbage  and  the  onion,  and  even  to  orange 
juice.  For  example,  25  c.c.  of  raw  swede  juice  were  equiva- 
lent to  1.5  gm.  of  raw  cabbage.  It  is,  therefore,  more 
potent  than  the  juice  of  raw  carrot,  and  far  more  effi- 
cacious than  the  juice  of  the  beet-root  (Table  3).  Tests 
carried    out   with  this    antiscorbutic    in  infant    feeding 

3  Dr.  Guy's  evidence,  Report  of  the  Lords  Commissioners  of  the  Ad- 
miralty on  the  Outbreak  of  Scurvy  in  the  Recent  Arctic  Expedition — 1877 
(cited   from  Chick  and  Hume). 

4  The  swede  is  a  root  vegetable  of  the  natural  order  Cruciferae.  It  is 
grown  to  a  large  extent  in  England,  but  is  practically  unknown  in  the 
United  States. 


ANTISCORBUTIC  FOODS  163 

seemed  to  show  that  it  is  of  value  in  this  field.  The 
authors  believe  that  the  potency  of  vegetables  is  closely- 
associated  with  certain  botanical  species,  and  that  in  this 
way  the  marked  virtue  of  the  swede  can  be  explained,  as 
it  belongs  to  the  natural  order  of  Cruciferae,  which  in- 
cludes also  the  cabbage,  the  scurvy  grass  and  the  cresses. 
If,  however,  this  is  a  rule  of  nature,  it  is  difficult  to  ex- 
plain the  marked  difference  between  the  lime  and  the 
lemon,  which  are  both  varieties  of  Citrus  Medica. 

Dehydrated  Vegetables. — For  hundreds  of  years  fresh 
vegetables  have  been  dried  to  serve  as  food  during  the 
winter  months  and  have  fulfilled  a  useful  purpose  on 
account  of  their  small  bulk  and  great  food  value.  The 
question  for  us  to  consider,  however,  is  whether  dehy- 
drated vegetables  still  retain  their  antiscorbutic  quality 
and  can  be  counted  on  to  supply  this  factor  in  the  dietary. 
At  present  this  subject  is  engaging  the  attention  of  labora- 
tory workers  as  well  as  of  practical  dietitians  and  food 
hygienists.  The  experience  of  the  past  is  not  happy  in 
this  regard.  In  the  Medical  and  Surgical  History  of 
the  War  of  the  Rebellion  we  read  as  follows :  "  A  scorbutic 
tendency  was  developed  at  most  of  our  military  posts  dur- 
ing the  winter  season,  after  the  troops  had  been  confined 
to  the  use  of  the  ordinary  ration  with  desiccated  vege- 
tables. The  latter  in  quantities  failed  to  repress  the  dis- 
ease. "  In  spite  of  this  and  similar  military  experiences  r> 
the  employment  of  dehydrated  vegetables  was  urged  re- 
cently for  rationing  our  soldiers,  the  claim  being  made 
that  "by  simply  soaking  in  water  and  boiling  in  the 

5 "  We  find  the  College  of  Physicians  at  Vienna  sent  to  Hungary  great 
quantities  of  the  most  approved  antiscorbutic  herbs  dried  in  this  manner; 
which  were  found  to  be  of  no  benefit.  Many  of  these  would  have  their 
virtues  as  little  impaired  by  drying  as  spinag^e,  e.g.,  marsh  trefoil.  Kramer 
tried  almost  every  species  of  dried  herbs  to  no  purpose."  (Treatise  on  The 
Scurvy.     James  Lind,  London,  1772,  p.  143.) 


164 


SCURVY:    PAST  AND  PRESENT 


same  water  these  vegetables  are  brought  back  to  the  con- 
dition of  fresh  vegetables."  Both  in  this  country  and  in 
England  there  was  strong  propaganda  during  the  war  to 
dehydrate  vegetables  on  an  enormous  scale  and  to  substi- 
tute them  for  the  fresh  food. 

Experimental  investigation  on  this  subject  may  be 
summarized  as  showing  that  vegetables  dried  according 


Period  I 
Hay,  oats,  water  ad 
libitum  plus  dehydrated 
6m.  carrots  (Tffm  daily) 


Period  JL- 

rreah  carrots  (335m. daily) 
substituted  tor  dehydrated  carrot* 


Fig.  12. — Hay,  oats,  water  ad  libitum,  and  7  gm.  of  dehy- 
drated carrots  dried  at  a  room  temperature  of  about  130°  F. 
about  1  month  previously.  All  animals  developed  scurvy. 
The  marked  gain  in  weight  when  an  equivalent  amount  of 
fresh  carrots  was  substituted  for  the  dehydrated  vegetable 
corresponded  to_  the  disappearance  of  scorbutic  signs. 
Guinea  Pig  B  951  did  not  receive  fresh  carrots,  as  it  was 
evidently  ailing  at  the  time  the  second  period  began. 

to  present  methods  lose  their  antiscorbutic  value  as  the 
result  of  dehydrating  (Fig.  12),  and  that  they  become 
still  more  impoverished  as  the  result  of  aging.  We 
should  not  sweepingly  condemn  the  principle  of  dehydra- 
tion, as  very  possibly  some  slight  modifications  in  the 
process  may  be  devised  which  will  counteract  the  de- 
teriorating influence.  In  their  paper  of  1912,  to  which 
reference  has  been  made  so  often,  Hoist  and  Froelich 


ANTISCORBUTIC  FOODS  165 

reported  that  potatoes,  carrots,  peas,  lentils  and  almonds 
have  practically  no  protective  value  after  they  are  thor- 
oughly dried.  In  two  reports — one  giving  the  results  of 
feeding  various  brands  of  dehydrated  carrots  to  guinea- 
pigs,  and  the  other  of  an  attempt  to  cure  scurvy  in  babies 
by  means  of  these  carrots — we  also  came  to  the  conclusion 
that  the  antiscorbutic  factor  had  been  almost  completely 
destroyed.  Givens  and  Cohen  (1918)  found  that  even 
cabbage  dried  at  a  low  temperature  retained  only  a  small 
amount  of  its  potency  after  a  month,  and  Delf  and  Skelton 
came  to  practically  the  same  conclusion,  also  noting  that 
the  cabbage  on  being  kept,  steadily  lost  what  little  of  the 
antiscorbutic  factor  had  survived  the  drying  process.  The 
same  was  true  of  the  fat-soluble  factor.  These  authors 
made  an  observation  which  may  prove  of  value  in  helping 
to  solve  this  problem,  namely,  that  "the  residual  amount 
is  distinctly  greater  if  the  cabbage  is  plunged  into  boiling 
water  before  drying."  This  protective  action  of  heat 
they  suggest  may  indicate  that:  "Some  at  least  of  the 
destruction  may  be  due  to  the  activity  of  an  enzyme  or 
other  body  originally  present  in  the  living  tissue/ ' 

Another  observation  which  may  prove  of  practical 
value  in  rendering  dehydrated  vegetables  the  nutritional 
equivalent  of  the  fresh  vegetable  is  that  when  the  carrots 
selected  for  dehydration  are  young  and  fresh  a  product 
is  obtained  which  possesses  decided  antiscorbutic  power. 
In  this  connection  the  following  statement  by  Falk  and  his 
co-workers  in  a  study  of  the  enzyme  action  of  vegetables 
and  the  effect  of  dehydration  is  significant:  "In  consider- 
ing these  enzyme  results,  it  may  be  pointed  out  that  the 
state  of  ripeness  and  the  age  of  the  vegetable  undoubtedly 
influence  the  activities. ' ' 

The  most  promising  dehydration  experiment  has  been 


166 


SCURVY:    PAST  AND  PRESENT 


conducted  by  Hoist  and  Froelich  and  was  published  in 
1916  in  a  paper  which  has  passed  unnoticed.  They  dried 
white  cabbage  so  that  it  retained  its  antiscorbutic  proper- 
ties, and,  to  a  large  extent,  its  color  and  taste,  for  a  period 
of  two  years.  This  result  was  accomplished  by  keeping 
out  all  moisture  and  preventing  hydrolysis,6  a  method 
which  is  employed  in  preserving  antitoxins,  toxins  and 
agglutinins.  It  is  by  far  the  most  encouraging  test  re- 
ported, and  should  be  made  the  basis  of  further  work  by 
those  actively  interested  in  perfecting  dehydration. 


Prune  Juice. 


Canned  Tomato. 


i 


i! 


iEE 


ll\ 


E 


il 


Fig.   13. — Cure  of  scurvy  by  the  addition  of  canned  tomato.     In  this  case,  as  frequently, 
the  alleviation  of  symptoms  preceded  the  gain  in  weight. 

Canned  Food  (Tomatoes). — In  the  course  of  canning,  as 
in  dehydrating,  most  vegetables  and  fruits  lose  their  anti- 
scorbutic properties.  A  general  denunciation,  however, 
of  all  canned  foods  is  incorrect,  as  there  are  exceptions 
to  this  rule.    It  has  been  shown  by  Hess  and  Unger  that 

9  The  cabbage  was  subjected  to  a  preliminary  drying  for  8  days  at 
37°  C.  It  was  then  put  in  an  air-tight  desiccator  which  contained  a  dish  of 
phosphorus  pentoxid.  [The  pentoxid  was  replaced  for  several  weeks  until  it 
ceased  to  liquefy.]  It  was  then  placed  in  cylinders  which  had  been  rendered 
air  free  by  means  of  a  suction  pump  and  which  contained  phosphorus  pent- 
oxid. This  was  kept  at  37°  C.  and  examined  after  10,  18  and  26  months. 
A  similar  result  was  not  obtained  when  calcium  chlorid  was  employed,  the 
temperature  held  at  37°  C.  and  the  cabbage  was  kept  in  an  air-tight  cylinder 
rather  than  in  a  vacuum.  However,  under  these  conditions  if  the  cabbage 
was  placed  in  the  ice  box  at  a  temperature  of  4°,  10°  or  12°  C.  the  antiscor- 
butic property  was  conserved  after  boiling. 


ANTISCORBUTIC  FOODS  167 

canned  tomatoes  possess  a  high  degree  of  antiscorbutic 
power  (Fig.  13),  and  it  is  probable  that  most  of  the 
acid  fruits  and  vegetables  are  able  to  withstand  the  can- 
ning process.  It  was  found,  in  an  experiment  embracing 
many  series  of  guinea-pigs,  that  4  c.c.  daily  of  strained, 
canned  tomato  are  sufficient  to  afford  protection,  even 
when  a  lot  was  used  which  had  been  prepared  a  year  pre- 
viously. This  is  indeed  remarkable,  considering  that  the 
food  undergoes  a  twofold  heating  in  the  course  of  can- 
ning, during  one  of  which  ("processing")  the  temperature 
is  raised  to  fully  230°  F.  Tomatoes  have  another  advan- 
tage over  most  other  vegetables  in  that  they  are  richly 
endowed  with  the  water-soluble  vitamine,  as  shown  by  our 
tests  on  pigeons  suffering  from  polyneuritis,  and  by  the 
experiments  on  rats  of  Osborne  and  Mendel,  who  found 
tomatoes  far  superior  in  this  respect  to  turnips,  onions, 
beet-roots  or  beans.  They  are  also  rich  in  the  fat-soluble 
vitamine.  In  view  of  the  availability  of  canned  tomatoes 
and  their  excellent  keeping  quality  they  are  well  suited  to 
an  extended  use  as  an  antiscorbutic.  In  the  subsequent 
chapter  we  shall  discuss  their  employment  in  infant  feed- 
ing and  in  the  army  ration. 

Germinated  Cereals  and  Pulses. — In  1912  Fuerst  reported 
that  although  the  resting  seed — the  cereal  grain,  the  pea, 
bean  and  lentil — are  poor  in  antiscorbutic  vitamine,  they 
develop  this  principle  as  soon  as  they  germinate.  They 
possess,  in  other  words,  latent  antiscorbutic  properties, 
and  are  potentially  antiscorbutic.  This  observation  is  not 
only  of  scientific  interest  but  of  practical  value,  as  these 
pulses  are  well  suited  for  transport  and  do  not  readily 
deteriorate.  For  this  reason,  Chick  and  her  co-workers 
at  the  Lister  Institute,  who  were  searching  for  an  anti- 


168  SCURVY:    PAST  AND  PRESENT 

scorbutic  foodstuff  for  the  army,  directed  their  attention 
to  the  utilization  of  the  pulses.  In  the  course  of  a  thor- 
ough investigation  (1919)  they  found  that  although  it  re- 
quired 30  to  40  g.  daily  of  diy  green  peas  to  prevent 
scurvy  in  the  guinea-pig,  a  consumption  of  10  g.  of  the 
germinated  peas  afforded  satisfactory  protection.7  The 
soaked  seeds  have  an  antiscorbutic  value  comparable  to 
many  of  the  fresh  vegetables ;  by  no  means  as  great  as 
cabbage,  but  somewhat  greater  than  that  of  carrots.  As 
the  result  of  cooking,  their  potency  was  found  to  be  re- 
duced about  75  per  cent.  We  shall  have  occasion  to  refer 
to  this  antiscorbutic  food  in  the  chapter  on  treatment  in 
connection  with  the  rationing  of  armies. 

Meat  and  Eggs. — As  has  been  stated,  animal  tissues  are 
distinctly  inferior  to  fruits  and  vegetables  in  the  anti- 
scorbutic principle.  As  there  has  been  no  accurate  evalua- 
tion of  these  foods — the  only  test  being  one  by  Chick, 
Hume  and  Skelton,  where  10  c.c.  or  raw  beef  juice  failed 
to  protect  guinea-pigs — we  have  to  depend  upon  clinical 
experience  for  our  knowledge.  Beef  juice  is  highly  rated 
by  physicians  in  the  prevention  of  infantile  scurvy,  but 
it  is  probably  far  less  potent  than  vegetables  or  fruit 
juices.  The  Arctic  explorers,  and  many  who  have  lived  in 
the  Arctic  regions,  agree  that  the  inhabitants  are  protected 
from  scurvy  during  the  winter  months  by  their  diet  of 
fresh  meat  and  fish.  The  Admiralty  Enquiry  on  the  out- 
break of  scurvy  in  the  Arctic  Expedition  of  1875  reported 
that  a  large  ration  of  meat  is  necessary  to  afford  protec- 
tion. Curran  (1847)  described  three  cases  admitted  to 
the  hospital  in  the  great  Irish  epidemic  of  that  year,  where 

7  The  pulses,  after  having  been  soaked  in  water  for  24  hours,  were 
kept  moist,  with  access  of  air,  for  about  48  hours  at  room  temperature, 
and  during  this  time  germinated,  developing  a  radicle  usually  about  1  cm. 
in  length. 


ANTISCORBUTIC  FOODS  169 

the  diet  previously  had  included  three-quarters  of  a  pound 
of  meat  on  five  days  of  the  week.  From  these  and  similar 
experiences  the  conclusion  is  manifest  that  the  divergence 
of  opinion  regarding  the  value  of  meat  is  based  upon  quan- 
titative differences  in  the  rations.  Evidently,  if  sufficient 
meat  is  provided,  the  development  of  scurvy  will  be  ob- 
viated. Another  factor  which  must  be  borne  in  mind  is 
that  those  who  refer  to  meat  in  the  Arctic  regions  refer  to 
fresh  raw  meat,  which  is  a  far  more  valuable  antiscorbutic 
than  the  ordinary  cooked  meat. 

There  is  almost  no  experimental  data  on  the  antiscor- 
butic value  of  eggs.  Hard-boiled  eggs  were  fed  to  guinea- 
pigs  and  it  was  found  that  9  g.  per  capita  daily  was 
insufficient  to  protect  them.  An  attempt  was  also  made 
to  cure  infantile  scurvy  with  a  daily  addition  of  one  raw 
egg  to  the  dietary,  but  without  avail.  It  is  possible  that 
fresh  raw  eggs  have  an  antiscorbutic  value  comparable  to 
meat,  but  the  large  quantity  required  makes  dependence 
upon  them  impracticable. 

Beer  and  Alcoholic  Beverages. — For  generations  beer  has  I 
been  highly  regarded  as  an  antiscorbutic.  Captain  Cook 
prized  it  greatly  and  always  supplied  his  men  with  a 
freshly-made  infusion  of  malt  called  "sweetwort."  Lind 
writes:  "Beer  and  fermented  liquors  of  any  sort  will  be 
found  the  best  antiscorbutic  remedies"  (p.  76).  He  re- 
fers at  different  times  to  the  value  of  spruce  beer,  ale,  wine 
and  other  vinous  liquors.  In  his  excellent  book  on  ' '  Mili- 
tary Hygiene,"  Munson  writes:  "Good  beer  and  wine 
have  decided  value,  also  vinegar."  On  the  other  hand, 
recent  scientific  experiment  has  shown  that  beer  has  prac- 
tically no  antiscorbutic  value.  There  is  but  one  study  on  I 
this  subject,  that  of  Harden  and  Zilva,  which  is  quite  con- 


170  SCURVY:    PAST  AND  PRESENT 

vincing.  They  found  that  guinea-pigs  and  monkeys  de- 
veloped scurvy  in  spite  of  the  fact  that  they  received, 
respectively,  50  c.c.  and  180  c.c.  of  beer  daily.  They  con- 
clude, as  a  result  of  their  experiments,  that  "bottled  ale 
and  stout  and  fined  beer  as  brought  on  to  the  market,  are 
lacking  both  in  antineuritic  and  antiscorbutic  accessory 
factors,  and  that  kilned  material  is  also  wanting  in  these 
two  principles."  The  apparent  contradiction  between 
practical  experience  and  laboratory  investigation  in  re- 
gard to  beer  is  due  to  a  difference  in  the  process  of  brew- 
ing. Cook  and  Lind  and  the  older  authors  refer  to  freshly- 
made  beer,  whereas  the  modern  beer  which  was  tested  in 
the  laboratory  was  made  from  l  i  high-dried ' '  material. 
The  antiscorbutic  potency  of  beer  as  formerly  used  was 
due  to  its  preparation  from  freshly-germinated  grain  and 
its  consumption  shortly  after  brewing.  Dyke  tells  us  of 
an  interesting  incident  illustrating  the  importance  of  this 
distinction.  In  the  recent  war  an  outbreak  of  scurvy 
occurred  among  the  Kaffir  labor  battalion  in  France.  At 
home  these  natives  consume  a  large  amount,  as  much  as 
three  gallons  a  day,  of  Kaffir  beer,  which  is  made  from 
freshly-germinated  corn,  and  is  consumed  shortly  after 
it  is  made.  The  French  prepared  a  similar  fermented 
beverage  for  their  South  African  laborers,  the  sole  differ- 
ence in  preparation  being  that  the  process  of  germination 
had  been  omitted  for  reasons  of  convenience.  Scurvy 
resulted,  a  disorder  which  is  practically  unknown  among 
the  natives  at  home. 

Miscellaneous  Foodstuffs. — During  the  past  few  years  a 
great  many  different  kinds  of  foods  have  been  tested 
iu  the  laboratory  for  their  antiscorbutic  value.  It  will 
be  well  for  completeness '  sake  to  say  a  word  about  them, 


ANTISCORBUTIC  FOODS 


171 


although  they  have  been  found  to  possess  little  or  no 
antiscorbutic  properties.  The  studies  of  Hoist  and 
Froelich  showed  definitely  that  all  the  cereals — oat,  bar- 
ley, rye,  maize,  and  preparations  made  from  the  bran 
or  from  the  endosperm — are  devoid  of  antiscorbutic  vita- 
mine.  Cohen  and  Mendel  added  3  per  cent,  of  calcium 
lactate  or  sodium  chloride,  or  5  per  cent,  of  butter,  without 
enhancing  the  value  of  oats  in  this  respect. 


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Fiq.   14. — Failure  of  yeast  as  a  prophylactic;  latent  scurvy  promptly  yielding  to  orange  juice. 


As  is  well  known,  yeast  possesses  the  water-soluble 
vitamine  in  marked  concentration.  It  is  natural,  there- 
fore, that  its  antiscorbutic  power  was  put  to  the  test, 
especially  as  it  has  been  accorded  therapeutic  value.  Hess 
and  Unger  showed  that  autolyzed  yeast  was  of  no  value 
in  the  cure  of  infantile  scurvy  (Fig.  14) ;  Chick  and  Hume 
(1917)  and  Cohen  and  Mendel  (1918)  came  to  the  same 


M~^ 


172  SCURVY:    PAST  AND  PRESENT 

conclusion  in  regard  to  guinea-pig  scurvy,  making  use  of 
autolyzed  yeast,  yeast  extract  and  dried  brewers '  yeast. 

In  view  of  the  fact  that  cod  liver  oil  is  practically  a 
specific  for  human  rickets,  Hess  and  Unger  tried  the  effect 
of  this  oil  both  in  infantile  scurvy  and  in  that  of  guinea- 
pigs.  It  proved  to  have  no  protective  or  curative  value. 
The  animal  experiments  were  confirmed  by  Cohen  and 
Mendel.    The  use  of  olive  oil  also  proved  futile. 

Pitz  in  1918  reported  that  in  animal  experiments  he 
had  found  that  lactose  was  able  to  protect  against  scurvy, 
and  attributed  this  result  to  its  power  to  alter  the  intes- 
tinal flora.  We  shall  not  enter  into  a  detailed  discussion 
of  this  question,  as  the  study  was  carried  out  on  a  ration 
embodying  unlimited  and  uncontrolled  amounts  of  milk, 
and  it  has  since  been  shown  that  the  apparent  cure  was 
due  to  an  increased  consumption  of  milk  by  the  animals 
in  the  progress  of  the  experiment.  Cohen  and  Mendel, 
Harden  and  Zilva,  Hart,  Steenbock  and  Smith  (1919  all 
failed  to  protect  or  to  cure  their  animals  with  lactose 
when  they  were  placed  on  a  ration  which  was  definitely 
measured  and  limited.  Hess  and  Unger  failed  to  cure 
infantile  scurvy  by  means  of  lactose. 

It  has  been  suggested  that  scurvy  is  due  to  a  lack  of 
secretion  of  the  endocrine  glands,  a  question  which  will 
be  referred  to  again  in  considering  the  relation  of  scurvy 
to  other  " deficiency  diseases."  With  this  idea  Ingier 
added  thyroid,  hypophysis,  thymus  and  parathyroid  to 
the  food  of  guinea-pigs,  or  gave  it  parenterally.  She  was 
unable  to  observe  any  beneficial  results.  Jackson  and 
Moore  met  with  the  same  result  on  feeding  desiccated  thy- 
roid gland.  We  may  add  that  we  gave  dried  thyroid 
and  also  parathyroid  glands  in  the  treatment  of  infantile 
scurvy  without  effect. 


ANTISCORBUTIC  FOODS  173 

CONCLUSIONS 

Any  consideration  of  the  question  of  antiscorbutic 
foodstuffs  brings  into  sharp  relief  the  difference  be- 
tween empiricism  and  scientific  investigation.  For  well 
over  a  hundred  years  it  was  generally  known  that 
scurvy  could  be  cured  by  fruits  or  vegetables,  and  yet  no 
further  progress  was  made  toward  a  more  complete 
understanding  of  the  value  of  these  foodstuffs.  As  far 
back  as  1847  Budd  ascribed  the  action  of  antiscorbutic 
foods  "to  an  essential  element,  which,  it  is  hardly  too 
sanguine  to  state,  will  be  discovered  by  organic  chemistry 
or  the  experiments  of  physiologists  in  a  not  far  distant 
future.' '  Busk,  in  giving  his  testimony  in  1877  before 
the  British  Scurvy  Commission,  said  that  it  was  his  be- 
lief "that  scurvy  was  due  to  the  fact  that  the  diet  was 
lacking  in  a  peculiar  and  as  yet  little  understood  factor. ' ' 
The  question  remained  in  this  hypothetical  and  inactive 
state  until  it  was  attacked  recently  by  experimental 
methods.  Decided  advance  has  been  made  only  in  the  past 
few  years,  since  these  foodstuffs  have  been  studied  from 
a  quantitative  viewpoint. 

The  antiscorbutic  factor  is  abundant  in  fresh  foods, 
especially  in  vegetables  and  fruits,  and  to  a  considerably 
less  extent  in  animal  foods,  such  as  milk,  meat  and  fish. 
Among  the  vegetables  there  is  a  marked  distinction  in 
potency.  A  beginning  has  been  made  in  standardizing 
these  various  foodstuffs,  in  grading  them  approximately 
according  to  their  antiscorbutic  efficacy  (Table  3).  It 
should  be  remembered,  however,  that  the  importance  of  an 
antiscorbutic  food  depends  not  only  on  its  intrinsic  con- 
tent of  the  antiscorbutic  factor,  but  quite  as  much  on  the 
amount  of  the  food  which  is  eaten.  For  example,  although 
potatoes  possess  only  moderate  virtue  compared  with 


174  SCURVY:    PAST  AND  PRESENT 

orange  juice,they  are  of  greater  practical  value  in  view  of 
the  large  quantities  which  are  consumed  and  their  avail- 
ability when  green  vegetables  are  lacking.  Furthermore, 
the  fact  recently  brought  out  that  the  various  vegetables, 
and  perhaps  the  fruits  as  well,  have  considerably  more 
value  when  they  are  fresh  and  young  than  when  they  are 
old,  warns  us  not  to  carry  our  quantitative  standardiza- 
tion too  far. 

Fruits  and  vegetables  which  are  dehydrated  have  been 
found  to  have  lost  their  antiscorbutic  properties.  This 
generalization  is  not  without  its  exception,  for  it  has  been 
found  that  cabbage  and  tomato  withstand  drying  well, 
and  that  if  milk  is  dried  under  favorable  conditions  it 
retains  a  very  large  part  of  its  antiscorbutic  value.  It 
may  be  stated  that  the  outlook  is  bright  in  regard  to 
dehydration,  as  the  problem  has  not  yet  been  thoroughly 
studied,  and  the  process  may  be  so  improved  that  there 
will  be  little  difference  in  the  nutritional  value  between  the 
fresh  and  the  dehydrated  food. 

The  study  of  antiscorbutic  values  points  a  lesson  in 
regard  to  the  methods  of  cooking  vegetables.  It  has 
demonstrated  that  short  cooking,  associated  with  a  high 
degree  of  temperature,  is  less  deleterious  than  longer 
cooking  at  a  low  degree.  In  other  words,  that  less  damage 
is  brought  about  by  boiling  or  by  steaming  vegetables 
than  by  stewing  them.  Here  age  and  freshness  again 
play  a  role ;  in  fact,  a  double  role,  as  the  older  and  tougher 
vegetables  contain  not  only  less  antiscorbutic,  but  require 
more  prolonged  cooking. 

In  general,  the  belief  is  correct  that  canning  destroys 
the  antiscorbutic  value  of  foods,  but  once  more  an  excep- 
tion must  be  made,  for  it  has  been  found  that  acid  foods, 


ANTISCORBUTIC  FOODS  175 

such  as  the  tomato,  withstand  the  canning  process  with 
but  little  loss  of  potency. 

The  field  of  antiscorbutic  foodstuffs  is  one  which  is 
fertile  for  future  investigation.  The  antiscorbutic  status 
of  milk  heated  to  various  heights  of  temperature  and  sub- 
jected to  various  degrees  of  aging  furnishes  problems 
of  great  practical  importance.  A  lack  of  growth  has 
been  noted  when  antiscorbutics  are  given  which  have  been 
subjected  to  a  high  degree  of  heat  {e.g.,  autoclaved  orange 
juice).  Whether  this  is  due  to  the  destruction  of  some 
other  growth  factor  is  a  question  which  has  been  raised 
by  several  experimental  studies  and  requires  an  answer. 

It  is  quite  possible  that  we  shall  find  useful  antiscor- 
butic foods  which  at  present  are  unknown  or  unappreci- 
ated. The  recent  introduction  of  the  swede,  of  the  canned 
tomato  and  of  germinated  pulses  suggests  and  even  ren- 
ders this  probable.  On  the  other  hand,  the  recognition  of 
the  comparative  poverty  of  the  antiscorbutic  factor  in 
lime  juice  shows  the  importance  of  putting  each  foodstuff 
to  the  experimental  test. 


CHAPTER  VII 
SYMPTOMATOLOGY  AND  DIAGNOSIS 

The  identity  of  scurvy  in  the  infant,  in  the  young  child 
and  in  the  adult  is  thoroughly  established  and  requires 
no  further  substantiation.  There  are,  however,  sufficient 
differences  between  the  symptoms  of  adult  scurvy  and 
those  of  Barlow's  disease  to  render  it  advisable  to  con- 
sider them  separately.  These  distinctions  are  due  largely 
to  the  fact  that  the  former  disorder  affects  mature  tissues, 
whereas  the  latter  is  engrafted  upon  tissues  which  are 
in  the  process  of  rapid  growth  and  development.  The 
symptomatology  is  influenced  also  by  the  striking  differ- 
ences in  environment — the  passive,  shielded  existence  of 
the  infant,  contrasted  with  the  active  and  exposed  life  of 
the  adult.  Although  we  shall,  therefore,' treat  adult  and 
infantile  scurvy  separately,  it  should  be  borne  in  mind 
that,  from  an  etiologic  and  pathologic  viewpoint,  such  a 
division  is  artificial  and  is  resorted  to  merely  for  pur- 
poses of  clarity. 

Adult  Scurvy. — The  earliest  sign  of  scurvy  is  usually 
a  change  in  the  complexion  of  the  individual.  His  color 
becomes  sallow  or  muddy,  an  aspect  difficult  to  describe, 
but  one  which  is  characteristic,  and  constitutes  an  im- 
portant danger  signal  to  the  eye  of  the  experienced  phy- 
sician. About  the  same  time  the  patient  loses  his  accus- 
tomed vigor,  seemingly  becomes  indolent  and  complains 
of  tiring  quickly,  and  of  breathlessness.  He  may  ex- 
perience fleeting  pains  in  the  joints  and  limbs,  especially 
in  the  legs,  symptoms  which  are  frequently  attributed  to 
rheumatism.    At  this  early  stage  the  appetite  may  still 

176 


SYMPTOMATOLOGY  AND  DIAGNOSIS  177 

be  normal,  there  is  usually  no  loss  in  weight,  but  merely 
a  general  malaise  which  is  significant,  although  in  no  way 
distinctive.  Very  soon  the  gums  become  sore,  bleed  read- 
ily, and  are  found  to  be  congested,  spongy,  and  somewhat 
hemorrhagic  at  their  edges.  Absolute  reliance  must  not, 
however,  be  placed  on  this  sign  for  early  diagnosis,  as 
at  times  it  does  not  appear  until  later.  Careful  examina- 
tion at  this  stage  will  disclose  petechial  spots  on  the  body, 
more  especially  on  the  legs,  at  the  site  of  the  hair-follicles, 
or  even  larger  ecchymoses,  depending  upon  the  hemor- 
rhagic tendency  of  the  individual,  his  exposure  to  bruis- 
ing, the  adequacy  of  his  diet,  and  secondary  infection. 
Less  frequently  bleeding  from  the  nose  occurs  early,  or 
the  eyelid  suddenly  becomes  swollen  and  purple,  or  the 
urine  shows  the  presence  of  blood. 

These  signs  progress  steadily  with  a  varying  degree 
of  rapidity.  The  complexion  becomes  more  dingy  and 
somewhat  brownish,  the  weakness  increases  so  that  the 
slightest  exertion  causes  breathlessness  and  palpitation, 
and  the  gums  become  spongy  and  even  fungous.  If  there 
is  infection  of  the  gums  and  the  teeth  are  carious,  the 
breath  is  extremely  foul — a  sign  long  associated  with 
scurvy.  Later  the  teeth  become  loose  and  may  fall  out, 
and  the  alveolar  process  undergoes  necrosis.  The  surface 
hemorrhages  increase  in  severity,  large  effusions  appear- 
ing on  the  trunk,  on  the  extremities,  and  less  often  be- 
neath the  mucous  membrane  of  the  mouth.  A  bloody 
diarrhoea  may  take  the  place  of  the  constipation  which  is 
generally  noted  earlier  in  the  disease.  There  are  at  this 
time  hemorrhages  into  the  muscles  and  deeper  tissues, 
especially  into  the  calves  of  the  legs,  giving  rise  to  hard, 
brawny,  tender  swellings  which  have  been  termed i  '  scurvy 
sclerosis."    This  is  sometimes  the  earliest  sign  noted  by 

12 


178  SCURVY:    PAST  AND  PRESENT 

the  patient  and  may  pnzzle  the  physician  who  has  not 
met  with  it  before.  The  swelling  may  be  found  in  the 
popliteal  space  or  at  the  site  of  the  tendo  Achilles,  and 
result  in  lameness  and  contracture  of  the  neighboring 
joint.  Frequently  there  is  slight  edema  of  the  ankles 
associated  with  a  glossiness  of  the  extensor  surfaces  of 
the  legs.  This  infiltration  differs  from  ordinary  edema 
in  being  firm  and  not  pitting  on  pressure.  The  skin  is 
dry  and  rough,  the  follicles  being  unusually  elevated;1 
the  hair  likewise  is  dry  and  loses  its  lustre.  Not  infre- 
quently subperiosteal  hemorrhages  occur,  giving  rise  to 
exquisitely  tender  swellings,  especially  of  the  tibia  or 
of  the  femur,  or  of  the  ramus  of  the  lower  jaw,  as  has 
been  noted  in  connection  with  guinea-pig  scurvy.  If  there 
are  wounds  or  ulcers  they  assume  a  hemorrhagic  aspect, 
the  edges  becoming  bluish  or  livid  and  showing  no  ten- 
dency to  heal;  even  scars  which  have  existed  for  many 
years  change  in  color  and  show  an  altered  state  of  nutri- 
tion, and  ulcers  long  healed  break  out  afresh. 

Nowadays,  the  disease  usually  does  not  reach  this 
stage,  and  rarely  progresses  further.  If,  however,  the 
patient  remains  untreated,  he  becomes  progressively 
weaker  and  more  lethargic ;  there  is  frequent  palpitation, 
shortness  of  breath,  and  increasing  loss  of  weight.  The 
pains  in  the  limbs  render  him  helpless  and  an  object  of 
pity.  Marked  edema  may  be  added  to  the  picture  as  the 
result  of  starvation,  so  that  the  legs  become  swollen, 
and  even  the  face  becomes  bloated.    Hemorrhages  into  the 

*As  the  result  of  an  experience  with  thousands  of  cases  of  scurvy 
in  the  Serhian  army,  Wiltshire  has  recently  laid  great  emphasis  on  this 
follicular  hyperkeratosis.  He  states  that  the  earliest  recognizable  sign  of 
scurvy  is  an  enlargement  of  the  hair  follicles  of  the  inner  and  anterior 
aspects  of  the  thigh  and  upper  leg,  which  show  numerous  conical  eleva- 
tions about  the  size  of  a  pin's  head.  A  hair,  broken  or  unbroken,  frequently 
pierces  the  follicle. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  179 

skin  as  large  as  the  palm  of  the  hand  appear  on  different 
parts  of  the  body.  The  gums  swell  to  such  an  extent  that 
they  overlap  and  may  even  hide  the  teeth  and  protrude 
from  the  mouth  as  foul  fungoid  growth.  Death  comes 
about  in  various  ways.  Frequently  sudden  and  fatal 
syncope  occurs,  due  to  heart  weakness  or  to  the  pouring 
out  of  fluid  into  the  pleural  or  the  pericardial  cavities. 
Another  frequent  cause  of  death  is  secondary  infection, 
resulting  in  pneumonia,  which  finally  ends  the  suffering  of 
the  patient.  The  fatal  outcome  is  thus  described  in  the 
narrative  of  Lord  Anson's  voyage: 

"Many  of  our  people,  though  confined  to  their  ham- 
mocks, ate  and  drank  heartily,  were  cheerful,  and  talked 
with  much  seeming  vigor,  and  in  a  loud,  strong  tone  of 
voice ;  and  yet,  on  their  being  the  least  moved,  though  it 
was  only  from  one  part  of  the  ship  to  another,  and  that 
in  their  hammocks,  they  have  immediately  expired;  and 
others,  who  have  confided  in  their  seeming  strength,  and 
have  resolved  to  get  out  of  their  hammocks,  have  died 
before  they  could  well  reach  the  deck.  And  it  was  no 
uncommon  thing  for  those  who  could  do  some  kind  of  duty, 
and  walk  the  deck,  to  drop  down  dead  in  an  instant,  on  any 
endeavor  to  act  with  their  utmost  vigor;  many  of  our 
people  having  perished  in  this  manner  during  the  course 
of  this  voyage. ' ' 

The  disease  may  develop  and  progress  in  various 
ways.  It  may  remain  latent  for  a  long  period  and  be 
cured  by  some  accidental  change  of  diet,  or,  as  more  fre- 
quently occurs,  it  runs  a  moderately  acute  course,  and  is 
promptly  cured  by  means  of  antiscorbutics.  In  the  days 
when  scurvy  was  common  and  widespread  it  sometimes 
became  chronic,  developing  into  the  "inveterate  scurvy' ' 


180  SCURVY:    PAST  AND  PRESENT 

of  the. older  authors,  which  was  notably  resistant  to  treat- 
ment. Harvey,  in  his  treatise  published  in  1685,  states 
that ' '  a  mild  scurvy  may  continue  or  be  protracted  to  ten, 
twenty,  or  thirty  years." 

In  addition  to  the  general  picture  of  the  disease  which 
we  have  presented,  mention  should  be  made  of  other  less 
common  symptoms.  As  is  well  known,  one  of  the  charac- 
teristic signs  of  scurvy  is  hemorrhage.  Indeed,  in  many 
of  the  systematic  treatises  of  medicine  it  is  classified  as 
a  hemorrhagic  disease.  Besides  the  bleeding  into  the 
gums,  skin  and  bones,  hemorrhage  into  the  stomach  may 
take  place,  giving  rise  to  hsematemesis,  or  there  may  be 
hemorrhage  into  the  eye,  under  the  conjunctiva  or  into 
the  anterior  chamber,  leading  to  the  destruction  of  the 
eyeball.  A  very  unusual  form  is  meningeal  bleeding, 
giving  rise  to  symptoms  of  apoplexy.  It  may  be  stated 
in  general  that  hemorrhage  dominates  the  picture  of 
scurvy.  Eruptions  which  in  normal  individuals  are  sim- 
ply macular  or  papular,  assume  a  hemorrhagic  character 
when  occurring  in  a  scorbutic  individual.  This  phenom- 
enon was  noted  in  the  recent  war  in  connection  with  the 
eruption  of  typhus  fever,  and  has  been  observed  by  mili- 
tary and  naval  surgeons  in  numerous  expeditions. 

Scurvy  reduces  the  nutritional  state  of  probably  all 
the  cells  and  tissues  of  the  body.  If  the  resistance  is 
still  further  lowered  by  exposure,  nutritional  disturb- 
ances will  result  more  readily  than  where  the  tissues  are 
normal  and  well-nourished.  For  this  reason  we  believe 
that  scurvy  may  predispose  to  frostbite.  Reports  of  con- 
gelations occurring  in  the  trenches  in  the  course  of  the 
World  War  tend  to  confirm  our  opinion  that  scurvy  was 
a  predisposing  factor  in  many  of  these  cases.  This  has 
been  true  in  other  wars.    For  example,  Munson  writes 


SYMPTOMATOLOGY  AND  DIAGNOSIS  181 

that '  'during  the  Crimean  War  the  temperature  was  never 
very  low  and  a  report  of  the  times  suggests  that  the  large 
number  of  congelations  observed  among  the  soldiers 
might  well  be  regarded  as  gangrene  owing  to  a  scorbutic 
tendency  exaggerated  by  the  cold. ' ' 

In  connection  with  the  involvement  of  the  gums,  an- 
other typical  symptom  of  scurvy,  it  should  be  remem- 
bered that  this  sign  may  appear  late  and  therefore  fail  to 
be  of  value  for  early  diagnosis,  and  that  it  occurs  also 
in  purpura  and  thus  may  lead  to  error.  This  is  especially 
the  case  if  there  is  pyorrhoea.  As  is  well  known,  hemor- 
rhages of  the  gums  appear  only  where  teeth  are  present, 
and  are  absent  in  the  edentulous  gums  of  old  people  as 
well  as  in  babies  who  have  no  teeth.  Immerman  is  prob- 
ably correct  in  believing  that  an  injury  is  always  neces- 
sary to  produce  a  hemorrhagic  lesion  in  scurvy,  and  that 
this  explains  the  early  involvement  of  the  gums  and  also 
their  non-implication  in  the  absence  of  teeth. 

It  is  a  common  belief  that  separation  of  the  epiphyses 
occurs  only  in  infants  and  young  children,  and  not  in 
the  scurvy  of  adults.  This,  however,  is  not  correct,  as  in 
severe  adult  scurvy  there  is  frequently  a  separation  of  the 
epiphyses  of  the  long  bones  of  the  lower  extremities  or 
of  the  ribs,  the  latter  resulting  in  a  sinking  of  the  sternum. 

The  pulse  is  sometimes  slow  and  feeble,  having  been 
recorded  as  low  as  40  beats  per  minute,  but  more  fre- 
quently is  rapid,  in  the  neighborhood  of  140.  It  is,  how- 
ever, almost  invariably  unduly  excited  by  emotion  or  by 
mild  physical  activity.  Frequently  there  is  a  low  type  of 
fever,  which  has  been  termed  "scorbutic  fever,"  but 
which  probably  should  be  regarded  as  a  complication  of 
the  disease  rather  than  as  an  intrinsic  symptom. 

There  is  little  tendency  to  the  formation  of  pus.    Al- 


182  SCURVY:    PAST  AND  PRESENT 

though  the  lymphatic  glands  are  frequently  enlarged  and 
effusions  into  the  tissues  and  into  cavities  of  the  body 
are  by  no  means  uncommon,  they  show  little  tendency  to 
become  purulent.  In  the  severe  cases  described  by  the 
older  authors,  the  breaking  down  of  the  glands  in  the  in- 
guinal region — buboes — is  frequently  noted.  The  urine  is 
apt  to  be  scanty,  becoming  much  more  profuse  following 
treatment.    Perspiration  is  also  retarded. 

A  peculiar  symptom  reported  in  connection  with 
numerous  epidemics  of  scurvy,  both  on  sea  and  on  land,  is 
nyctalopia  or  night-blindness.  The  patients  can  see  fairly 
well  during  the  day,  but  have  very  little  vision  as  soon  as 
darkness  develops.  This  phenomenon  has  puzzled  many 
observers,  as  nothing  abnormal  has  been  found  on  exam- 
ination of  the  eyes.  Recently  0  'Shea,  who  met  with  many 
cases  of  this  nature  among  soldiers,  has  reported  that  in 
an  ophthalmic  examination  of  22  cases  the  only  abnor- 
mality was  pallor  of  the  optic  disc  in  3  cases.  This 
weakness  of  sight  is  due  to  the  general  nutritional  weak- 
ness and  has  been  reported  in  connection  with  other  ex- 
hausting and  nutritional  diseases — for  example,  hunger 
edema.    More  rarely  there  is  day-blindness. 

As  a  complication,  dysentery  may  be  mentioned.  This 
has  been  described  by  Schreiber  and  others  in  scurvy  epi- 
demics occurring  in  the  course  of  the  World  War.  Jaun- 
dice may  appear,  and  might  be  expected  to  occur  more 
often  in  view  of  the  marked  congestion  of  the  upper  duo- 
denum found  so  frequently  at  necropsy. 

Pericarditis,  hydrothorax,  pleurisy  with  effusion, 
pneumonia,  are  common  complications  of  severe  forms  of 
scurvy.  Lind  reports  that  the  dominant  complication 
varies  in  different  epidemics;  that  on  one  cruise  many 


SYMPTOMATOLOGY  AND  DIAGNOSIS  183 

cases  of  diarrhoea  would  occur  and  on  another  many  pul- 
monary infections. 

0  'Shea  reports  the  exceptional  case  of  a  man  who  was 
operated  upon  for  acute  appendicitis.  A  large  hemor- 
rhage in  the  wall  of  the  caecum  was  found,  as  well  as  some 
other  hemorrhages  in  the  peritoneal  cavity.  This  report 
is  interesting,  not  so  much  from  a  diagnostic  standpoint 
as  because  "  contrary  to  what  might  have  been  expected, 
scorbutic  cases  when  operated  upon  showed  no  particular 
tendency  to  hemorrhage." 

Infantile  Scurvy. — The  stereotyped  picture  of  infantile 
scurvy  and  the  one  which  this  term  commonly  suggests, 
is  that  of  the  acute  form  of  the  disease.  In  acute  infan- 
tile scurvy  we  have  to  do  generally  with  a  poorly-nour- 
ished, pale  infant  with  a  peculiarly  alert  and  worried 
expression.  As  we  approach  its  bed  it  whimpers  or  cries 
out  in  terror.  Frequently  its  posture  is  characteristic,  as 
it  lies  quietly  on  its  back  with  one  thigh  everted  and  flexed 
on  the  abdomen.  Examination  shows  that  one  or  even 
both  thighs  are  swollen  and  exquisitely  tender,  or  that 
there  is  merely  tenderness,  the  baby  shrieking  at  the 
slightest  pressure  upon  the  lower  end  of  the  femur.  If 
teeth  are  present,  the  adjacent  gums  are  red,  swollen  and 
bleed  readily.  This  is  the  syndrome  which  the  medical 
student  is  taught  to  carry  away  to  guide  him  in  his  every- 
day practice.  It  is  the  acute,  florid  type,  and  presents  a 
striking  picture,  but  must  not  be  regarded  as  the  common 
form  of  the  disorder.  If  we  are  to  diagnose  infantile 
scurvy  early  and  not  overlook  its  more  subtle  manifes- 
tations, the  classic  textbook  description  must  be  aug- 
mented by  portrayals  of  types  of  the  disorder  which  are 
less  crude  and  more  difficult  to  recognize — of  " sub-acute' ' 
and  of  " latent"  scurvy. 


184  SCURVY:    PAST  AND  PRESENT 

The  commoner  form,  which  we  have  termed  "subacute 
infantile  scurvy,"  comprises  a  large  number  of  symptoms 
which  are  inconclusive  individually,  and  frequently  escape 
correct  interpretation.  The  affected  baby  is  usually  in  the 
second  half  of  the  first  year  of  life,  and  does  not  gain  in 
weight  or  gains  but  slightly  for  weeks.  It  may  be  fairly 
well  nourished,  but  is  pale  or  sallow,  with  perhaps  slight 
edema  of  the  upper  eyelids.  The  mother  or  nurse  com- 
plains that  the  child  is  irritable  and  peevish,  and  that  the 
appetite  is  poor  or  capricious.  The  gums  show  a  lividity 
or  slight  peridental  hemorrhage,  which  on  subsequent 
examination  may  be  no  longer  visible,  and  may  have  con- 
sisted merely  of  a  rim  of  crimson  edging  the  borders  of 
the  upper  gum,  perhaps  behind  an  upper  incisor,  as  Still 
pointed  out.  On  closer  examination  it  may  be  observed 
t3i at  the  papillae  of  the  tip  of  the  tongue  are  markedly  con- 
gested, and  that  a  petechial  spot  is  to  be  seen  on  its  frenum, 
on  the  palpebral  conjunctiva,  or  here  and  there  on  the 
surface  of  the  body,  more  especially  where  there  are  ero- 
sions, eczema  or  other  skin  lesions.  Attention  may  be 
called  to  tenderness  of  the  lower  thighs,  which  in  some 
instances  is  definite,  in  others  so  ill-defined  and  fleeting 
that  it  is  impossible  to  convince  oneself  of  its  significance 
or  even  reality.  There  may  be  slight  edema  over  the 
crests  of  the  tibia,  of  a  kind  which  does  not  pit  on  pressure. 
The  knee-jerks  are  almost  always  markedly  exaggerated. 
The  urine  is  diminished  in  volume  but  is  generally  normal 
or  contains  a  trace  of  albumen  and  red  and  white  blood- 
cells.  The  pulse  is  frequently  rapid,  and  becomes  mark- 
edly rapid  and  irregular  on  the  slightest  excitement.  The 
respirations  are  also  rapid  (Fig.  15). 

These  symptoms  do  not  constitute  a  rigid  entity,  but 
are  subject  to  manifold  variations.    The  syndrome  may 


SYMPTOMATOLOGY  AND  DIAGNOSIS  185 

be  rendered  less  typical  and  clear  by  the  fact  that  the 
infant  has  gained  steadily  rather  than  lost  in  weight,  as 
is  sometimes  the  case  if  the  food  has  been  insufficient 
during  the  first  few  months  of  life.  Koentgenograms  of 
the  bones  may  show  the  " white  line"  at  the  epiphyses  first 
described  by  Fraenkel  (Fig.  20)  or  a  thickening  of  the 
periosteum.  However,  too  great  reliance  should  not  be 
placed  on  these  signs  in  making  an  early  diagnosis  of  this 
disorder,  as  neither  is  invariably  present. 

An  instance  of  subacute  scurvy,  which  in  many  re- 
spects is  typical,  is  the  following : 

I.  F.,  girl,  was  seen  when  3  months  old,  weighing 
somewhat  over  8  pounds.  She  was  given  Schloss  milk, 
4  ounces,  and  then  5  ounces  every  three  hours,  and  did 
well,  weighing  11%  pounds  two  months  later.  As  she 
failed  to  gain  for  some  weeks,  although  getting  6  ounces 
of  food,  it  was  thought  that  this  might  be  due  to  the  fact 
that  she  was  getting  pasteurized  milk  and  had  never  re- 
ceived an  antiscorbutic.  Autolyzed  yeast  had  been  tried  as 
a  prophylactic  antiscorbutic,  but  failed  to  bring  about  a 
gain.  When,  however,  orange  juice  was  substituted  for  the 
yeast,  a  prompt  growth-reaction  resulted,  a  gain  of  1*4 
pounds  in  four  weeks.  Accompanying  this  lack  of  gain 
in  weight  there  were  many  of  the  other  symptoms  enu- 
merated above;  irritability,  pallor,  slight  tenderness  of 
the  lower  ends  of  the  femora,  albumin  and  a  few  red  and 
white  cells  in  the  urine.  The  pulse-  or  heart-beat  was  fre- 
quently over  150,  and  the  respiration  60  (Fig.  15).  The 
diagnosis  of  subacute  scurvy  was  substantiated  by  the 
prompt  subsidence  of  all  symptoms  when  orange  juice 
was  administered. 

Infantile  scurvy  may  be  dormant  for  a  long  time. 
The  diagnosis  of  latent  scurvy  is  based  mainly  on  the 


186 


SCURVY:    PAST  AND  PRESENT 


reaction  to  specific  therapy,  on  the  marked  improvement 
when  orange  juice,  tomato,  potato  or  other  antiscorbutic 
food  is  given.  The  symptoms  themselves  are  suggestive, 
and  do  not  enable  an  absolute  diagnosis  to  be  made.  In 
our  experience  with  many  cases  of  this  kind  the  usual 
course  has  been  as  follows :  The  infant  has  been  generally 
from  6  to  9  months  of  age,  and  fed  for  a  considerable 


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Fio.   15. — Chart  of  I.  F.,  aged  7  months,  showing  a  prompt  effect  on  pulse,  respiration  and 

temperature  of  substitution  of  orange  juice  (30  c.c.)  for  autolyzed  yeast  (30  c.c.)  and  a  further 

response  when  the  former  was  replaced  by  potato  (15  gm.). 

period  on  pasteurized  milk,  which  may  or  may  not  have 
been  prepared  with  cereal  decoction.  Nor  has  it  been 
material  whether  gruels  also  had  been  given.  When  about 
6  months  of  age  the  baby  ceased  to  thrive,  to  gain  satis- 
factorily, to  look  healthy,  and  to  feed  as  it  should.  The 
most  careful  investigation  or  physical  examination  has 
failed  to  solve  the  difficulty.  On  the  other  hand,  the  his- 
tory of  a  diet  of  heated  milk,  especially  if  the  quantity 


SYMPTOMATOLOGY  AND  DIAGNOSIS  187 

was  not  large,  considered  in  conjunction  with  the  pallor 
and  poor  appetite,  the  increased  knee-jerks,  and  perhaps 
a  rapid  pulse  and  respiration  (the  cardiorespiratory  syn- 
drome), has  awakened  suspicion.  Orange  juice  or  canned 
tomato,  prescribed  in  such  cases  with  a  view  to  diagnosis 
as  well  as  to  treatment,  frequently  brings  about  a  magic 
result.  The  following  case,  the  weight  chart  of  which  is 
reproduced  (Fig.  14),  is  fairly  typical  of  this  abnormal 
nutritional  state: 

H.  S.,  boy,  born  December  15,  1915,  was  artificially 
fed  until  January  4,  1916,  when  he  weighed  6y2  pounds. 
He  was  given  28  ounces  of  Schloss  milk  a  day.  (This 
was  prepared  from  pasteurized  milk  which  was  not  heated 
a  second  time.  It  contains  per  litre  (quart)  140  c.c.  of 
whole  milk,  140  c.c.  of  20  per  cent,  cream,  50  gm.  of  dex- 
trimaltose,  5  gm.  of  plasmon,  0.2  gm.  of  potassium  chlo- 
rate, and  700  c.c.  of  water.)  By  March  1  he  weighed  9 
pounds,  and  gained  three-quarters  of  a  pound  more  in  the 
course  of  this  month.  During  April  he  gained  only  4 
ounces.  As  will  be  seen  from  the  chart,  there  was  almost 
a  cessation  of  gain  from  April  10  to  May  3,  although  yeast 
was  added  to  the  diet.  May  2,  orange  juice  was  given. 
The  weight  advanced  at  once,  the  color  and  the  general 
appearance  improved,  and  an  eczematous  condition  of  the 
face  rapidly  healed.  It  will  be  noted  from  the  chart  that 
the  gain  occurred,  although  the  food  intake  remained 
the  same. 

Epicrisis :  A  baby  4  months  old  with  latent  scurvy, 
which  existed  since  he  was  at  least  3  months  of  age. 

This  condition  of  latent  scurvy  is  probably  the  com- 
monest type  of  the  disorder,  especially  in  the  larger  cities 
where  almost  the  entire  milk  supply  for  infants  is  pas- 
teurised.   It  usually  passes  unrecognized.    Most  infants 


188  SCURVY:    PAST  AND  PRESENT 

fortunately  are  given  orange  juice  by  the  time  they  are  6 
months  of  age,  and  may  receive  a  small  amount  of  vege- 
table or  potato  before  they  are  much  older,  so  that  they 
are  protected  from  serious  harm  in  this  way.  But  there 
is  no  doubt  a  considerable  number,  especially  those  pecu- 
liarly susceptible,  who  quite  unbeknown  to  anyone  pass 
through  the  state  of  latent  scurvy. 

If  this  large  group  of  cases  were  included  in  the  inci- 
dence of  infantile  scurvy,  we  should  not  look  upon  it  as 
a  disorder  which  occurs  rarely  during  the  first  six  months 
of  life. 

When  scurvy  goes  unrecognized  or  untreated  for  a 
long  time,  or  the  antiscorbutic  content  of  the  food  is 
exceptionally  small,  or  the  patient  unusually  susceptible, 
the  disorder  may  progress  and  resemble  the  advanced 
cases  described  in  connection  with  the  adult  type  of  this 
disease.  Happily  such  instances  are  rare.  One  of  the 
most  typical  and  vivid  descriptions  of  an  extreme  case 
of  infantile  scurvy  is  that  reported  by  Vincent: 

The  infant  lay  in  its  bed  extremely  apathetic  and 
barely  conscious.  Its  face  was  ashy  gray  in  color,  the 
respirations  were  extremely  frequent,  the  pulse-rate  was 
144  per  minute,  and  the  temperature  103.2°.  When 
touched  it  moaned  feebly,  and  made  no  attempt  at  move- 
ment. The  mouth  was  kept  open,  the  lower  jaw  hanging 
away  from  the  face.  There  was  a  complete  absence  of 
muscular  tone,  so  that  the  infant  appeared  to  be  quite 
incapable  of  voluntary  movement. 

The  mouth  presented  a  horrible  appearance.  No  sign 
of  the  teeth  could  be  discovered,  though  it  was  stated  that 
several  had  appeared.  All  that  could  be  seen  was  a  pur- 
ple mass,  which  was  so  extensive  that  on  superficial  inspec- 
tion it  was  difficult  to  distinguish  between  the  upper  and 


SYMPTOMATOLOGY  AND  DIAGNOSIS  189 

lower  jaws,  despite  their  wide  separation.  Scattered  over 
this  purple  mass  were  areas  of  necrosing  tissue,  the  odor 
of  which  was  extremely  unpleasant. 

Petechial  hemorrhages  were  distributed  over  the  back 
and  limbs,  and  a  large  patch  of  extravasated  blood  was 
found  in  the  region  of  the  left  hip. 

Tenderness  was  present  in  all  the  limbs,  as  manifested 
by  moaning  and  by  the  facial  expression.  There  was  a 
general  enlargement  over  both  humeri  throughout  their 
length;  the  ulna  and  radius  did  not  appear  to  be  thus 
affected,  but  the  index-finger  of  the  right  hand  was  en- 
larged, especially  at  the  junction  of  the  metacarpal  bone 
with  the  first  phalanx,  the  enlargement  being  at  each  side 
of  the  joint.  In  the  legs  the  signs  were  extreme.  At  both 
knee-joints  the  skin  was  tightly  stretched  over  the  swol- 
len epiphyses;  the  tenderness  also  was  greater  than  at 
any  other  part. 

Bleeding  from  the  gums  and  nose  had  occurred;  no 
history  of  hematuria  could  be  obtained.  The  motions 
were  semisolid,  green,  and  offensive.  During  the  last 
twenty-four  hours  the  infant  had  refused  food. 

The  baby  was  given  large  amounts  of  lemon  juice  and 
subcutaneous  injections  of  salt  solution  and  the  necro- 
sing surfaces  of  the  gums  were  scraped  and  swabbed  with 
boracic  solution.  By  the  third  day  the  pulse  was  100,  the 
temperature  99.8°,  the  odor  from  the  mouth  scarcely 
noticeable,  and  the  general  condition  distinctly  improved. 
It  continued  to  improve  and  to  gain  in  weight  and  when 
seen  at  the  end  of  the  sixth  week  of  treatment  it  was 
doing  well  and  was  quite  happy. 

It  will  be  well  to  consider  in  detail  the  signs  and  symp- 
toms which  may  develop  in  the  course  of  scurvy. 

Hemorrhage. — Hemorrhage  of  the  gums  is  one  of  the 
characteristic  signs  of  scurvy.  For  a  reason  not  clearly 
understood  it  involves  first  and  foremost  the  tissues  about 


190  SCURVY:    PAST  AND  PRESENT 

the  upper  incisors.  If,  however,  we  fix  our  attention  too 
narrowly  to  this  region  we  may  be  led  into  error ;  in  several 
instances  we  have  first  encountered  hemorrhages  about  the 
molar  or  the  canine  teeth,  which  had  been  overlooked  be- 
cause the  anterior  part  of  the  gums  had  been  found  normal. 
"Where  teeth  are  absent  or  not  in  the  course  of  eruption 
hemorrhages  do  not  appear.  At  the  onset  the  gums  may  be 
merely  deep  red  or  bluish  red,  especially  if  they  overlie 
upper  incisors  which  are  close  to  the  surface.  Hemor- 
rhage is  particularly  apt  to  occur  where  the  edges  of  the 
teeth  have  just  broken  through  the  mucous  membrane. 
In  this  connection  the  question  arises  as  to  whether  every 
hemorrhage  of  the  gums  in  infants  is  to  be  considered  a 
sign  of  scurvy.  This  is  a  matter  of  some  diagnostic  im- 
portance. We  have  seen  hemorrhages  of  the  gums  at  the 
site  of  erupting  molar  teeth  where,  as  prolonged  obser- 
vation proved,  not  even  latent  scurvy  existed.  This  sign 
should  not,  therefore,  be  regarded  as  pathognomonic.  In 
two  infants  entirely  free  from  scurvy  we  have  noted 
slight  hemorrhage  of  the  gums  overlying  incisor  teeth. 
It  should  be  well  understood  that  such  an  occurrence  is 
most  exceptional;  it  is  to  be  attributed  probably  to  bac- 
terial invasion  or  to  a  constitutional  hemorrhagic  con- 
dition.   One  of  these  cases  was  the  following: 

The  infant  was  Sy2  months  old.  It  had  been  nursed  by 
the  mother  up  to  this  time  and  was  well  nourished,  but 
when  first  seen  had  some  fever,  probably  due  to  a  grippe 
infection.  About  ten  days  later  distinct  linear  hemorrhages 
of  the  gums  were  noted  over  the  two  upper  incisor  teeth. 
No  treatment  was  instituted  for  this  condition,  and  it 
healed  within  a  week.  There  was  no  subsequent  sign  of 
similar  hemorrhage  or  of  other  scorbutic  manifestation 
in  the  months  that  the  baby  was  under  observation. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  191 

The  localization  of  the  hemorrhage  in  the  gums  is  due 
largely  to  trauma,  occasioned  by  the  sharp  contact  of  the 
jaws  or  of  the  nursing-bottle.  Local  infection  plays 
almost  no  role  in  infants,  although  in  the  adult  where 
there  is  caries  of  the  teeth  it  frequently  incites  hemor- 
rhage. Dental  caries  and  gingival  infection  may  lead  to 
local  hemorrhage,  even  where  the  nutritional  conditions 
are  normal. 

Subperiosteal  hemorrhage  is  a  sign  distinctive  of  infan- 
tile scurvy,  although  it  must  be  borne  in  mind  that  it  may 
take  place  in  the  scurvy  of  adults.  It  involves  most  fre- 
quently the  lower  end  of  the  femur  and  the  tibia,  but 
occurs  in  connection  with  the  humerus,  the  mandible,  the 
scapula  and  other  bones.2  The  hemorrhage  usually  mani- 
fests itself  as  a  swelling  which  appears  suddenly  at  the 
lower  end  of  the  femur  or  femora.  It  is  brought  about  by 
trauma,  at  times  in  the  course  of  diapering,  or  by  manipu- 
lation in  testing  for  local  tenderness.  The  swelling  is 
very  tender,  and  varies  in  size  from  an  enlargement  which 
is  difficult  to  appreciate,  to  one  which  renders  the  leg 
fully  twice  its  normal  circumference  (Fig.  18)  .  It  may 
involve  merely  a  small  part  of  the  long  bone  or  extend  up 
or  down  the  shaft  for  a  long  distance.  As  might  be  sup- 
posed from  the  nature  of  this  lesion,  the  enlargement  per- 
sists for  weeks,  frequently  long  after  the  gums  and  the 
general  symptoms  have  disappeared.  During  this  period 
it  becomes  harder  and  less  tender,  and  may  develop  the 

2  There  seems  to  be  some  misconception  as  to  the  pathogenesis  of  the 
subperiosteal  hemorrhage  in  scurvy.  In  most  reports  this  lesion  is  de- 
scribed as  if  it  resulted  from  a  hemorrhage  burrowing  its  way  beneath  the 
periosteum  and  raising  it  from  the  subjacent  bone.  In  point  of  fact,  such 
an  event  is  impossible,  as  will  be  fully  realized  when  one  experiences  the 
great  difficulty  in  separating  periosteum  from  normal  bone.  The  scorbutic 
process  involves  the  periosteum  so  that  it  is  no  longer  normal  but  becomes 
insecurely  attached  to  the  shaft  of  the  bone,  and  is  readily  stripped  off 
by  hemorrhage. 


192  SCURVY:    PAST  AND  PRESENT 

consistency  of  bone ;  it  is  in  this  stage  that  such  swellings 
have  been  diagnosed  as  new  growths,  and  that  incision  or 
even  amputation  of  the  leg  has  been  resorted  to.  In  sub- 
acute cases  the  swelling — which  must  be  regarded  as 
hemorrhagic  rather  than  scorbutic — may  be  absorbed 
gradually  in  spite  of  the  fact  that  no  antiscorbutic  food 
has  been  given.  This  has  led  to  the  mistaken  conclusion 
that  the  scurvy  has  been  cured  without  dietetic  treatment. 

Subperiosteal  hemorrhage  may  be  clearly  seen  by 
means  of  the  fluoroscope  or  in  X-ray  photographs  (Figs. 
16  and  17).  The  shaft  of  the  bone  appears  surmounted 
by  an  elongated  blood-clot,  which  is  more  or  less  distinct 
according  to  its  age  and  density.  It  may  become  calcined, 
as  clearly  seen  in  figures.  More  often  the  periosteum 
undergoes  calcification  or  ossification,  especially  near  the 
site  of  the  separation  of  the  epiphysis.  This  gives  rise 
to  a  bizarre  radiographic  picture  which  may  be  difficult 
to  interpret — the  opaque  strip  or  streamer  being  almost 
unrecognizable  as  periosteum  (Fig.  17). 

Hess  and  Unger  observed  that  in  several  instances 
where  subperiosteal  hemorrhage  had  been  diagnosed, 
X-ray  examination  disclosed  that  the  swelling  of  the  thigh 
was  due  mainly  to  infiltration  of  the  muscles  and  subcu- 
taneous tissue.  It  is  surprising  how  an  infiltration  of 
serum  gives  rise  to  a  swelling  which  resembles  in  appear- 
ance and  consistency  the  classical  subperiosteal  tumor. 

The  skin,  mucous  membranes  and  subcutaneous  tissues 
are  frequently  the  sites  of  hemorrhage.  There  is  a  differ- 
ence of  opinion  as  to  how  frequently  petechial  hemor- 
rhages occur  in  scurvy,  particularly  as  to  whether  they 
are  encountered  early  in  this  disorder.  Great  variation 
in  this  regard  may  be  noted  in  individuals  and  in  groups 
of  cases  occurring  at  different  times.    In  the  cases  re- 


Fig.   Ki. — Infant  11  months  old.    Separation  of  lower  epiphysis  of  femur.     Fraying  of  end 

of  femur  and  head  of  tibia.     Subperiosteal  hemorrhage  surrounding  lower  part  ot  shaft  ol 

femur,  with  calcification  of  periosteum  and  of  clot. 


Fia.   17.  — Infanl  11'..  months  old.    Separation  of  lower  epiphysis  of  femur  with  marked 

subperiosteal  hemorrhage.     Typical  periosteal  "tags"  or  "streamers."     The  connection 

>A  these  "streamers"  with  the  periosteal  layer  is  evident. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  193 

ported  in  1914  by  Hess  and  Fish,  petechial  hemorrhages 
were  frequently  an  early  sign,  to  such  an  extent  that  they 
led  to  a  study  of  the  blood  and  blood-vessels  in  this  dis- 
order. The  hemorrhages  in  this  "scurvy  epidemic' '  were 
the  result  of  a  complication  of  scurvy  with  an  infectious 
disease.  It  is  not  necessary,  however,  for  infection  to 
exist  to  bring  about  a  rupture  of  the  small  vessels.  The 
idiosyncrasy  of  the  individual  has  to  be  considered  as  well 
as  the  fact  that  infants  have  a  tendency  to  develop  minute 
skin  hemorrhages,  especially  such  as  have  an  exudative 
diathesis.  In  the  course  of  scurvy,  petechias  may  be  found 
not  only  in  the  skin,  but  in  the  mucosa  of  the  mouth,  espe- 
cially overlying  the  hard  palate,  and  also  in  the  palpebral 
conjunctiva,  identical  with  the  minute  petechiae  so  signifi- 
cant of  general  sepsis.  In  addition  to  these  minute  hemor- 
rhages larger  ones  are  not  infrequently  found  in  various 
parts  of  the  body,  especially  in  the  neighborhood  of  the 
joints.  They  appear  as  discolorations  of  various  intensi- 
ties and  shades,  and  are  often  interpreted  as  being  merely 
the  result  of  bruises.  These  have  been  encountered  most 
often  about  the  knee-joint,  on  the  forehead,  or  in  the 
concha  of  the  external  ear,  where  they  may  best  be  seen 
by  means  of  transmitted  light. 

A  form  of  hemorrhage  which  must  be  especially  men- 
tioned, although  it  is  very  infrequent,  is  that  taking  place 
into  the  orbit,  leading  to  a  proptosis  of  the  eyeball,  usually 
the  left  (Still).  This  sign  should  be  borne  in  mind,  as  it 
occurs  occasionally  before  other  symptoms  have  rendered 
the  diagnosis  clear,  and  may  lead  to  a  diagnosis  of  tumor. 

As  mentioned  above,  hemorrhages  into  the  muscles  or 
between  the  muscle  planes  are  very  common  in  adults, 
leading  to  hard  swellings,  the  typical  "scurvy  sclerosis.' ' 
Such  effusions  occur  much  less  frequently  in  infants,  due 

13 


194  SCURVY:    PAST  AND  PRESENT 

probably  to  their  lack  of  activity.  In  addition  to  these 
hemorrhages  there  are  serous  effusions  of  the  muscles 
similar  to  those  which  are  found  in  the  pleural  and  peri- 
cardial cavities.  These  effusions  are  very  striking  at 
necropsy,  when  one  incises  the  muscles — for  example, 
the  muscles  of  the  thigh.  During  life  they  are  frequently 
mistaken  for  subperiosteal  hemorrhages. 

Less  frequently  there  are  hemorrhages  into  the  inter- 
nal organs.  These,  however,  play  a  comparatively  insig- 
nificant role  in  the  symptomatology  of  this  disease.  At 
postmortem  examination  we  find  numerous  hemorrhages 
of  the  pleura,  pericardium  and  peritoneum,  which  rarely 
produce  symptoms  during  life.  Still  records  a  case  with 
marked  abdominal  pain  and  swelling,  which  he  believed 
to  have  been  due  to  hemorrhage  into  the  wall  of  the  intes- 
tine. As  previously  mentioned,  O'Shea  met  with  a  case 
of  hemorrhage  into  the  caecum  which  was  mistakenly  oper- 
ated upon  for  appendicitis.  Hemothorax  and  hsemoperi- 
cardium  occur,  especially  associated  with  local  inflamma- 
tory processes  of  tuberculous  nature.  The  clinical  aspect 
of  hemorrhage  of  the  gastro-intestinal  and  the  genito-uri- 
nary  tracts  will  be  considered  elsewhere. 

In  the  scurvy  of  adults  as  well  as  that  of  infants,  the 
nails  and  the  hair  are  altered  by  the  nutritional  condition. 
Mention  has  been  made  of  the  hyperkeratosis  recently 
emphasized  by  Wiltshire  as  an  early  sign,  occurring  espe- 
cially on  the  thighs  and  legs.  The  skin  is  frequently  dry, 
the  so-called  " goose  skin"  that  is  seen  in  some  poor 
nutritional  states.  The  nails  are  thin,  brittle  and  lined; 
at  times  small  hemorrhages  will  be  noted  beneath  them. 
The  hair  also  becomes  thin  and  dry,  and  there  is  a  ten- 
dency for  petechial  hemorrhages  to  develop  at  the  roots. 

In  a  paper  on  the  therapeutic  value  of  yeast  and  of 


SYMPTOMATOLOGY  AND  DIAGNOSIS  195 

wheat  embryo  the  author  called  attention  to  the  fact  that 
eczema  may  occur  in  connection  with  infantile  scurvy, 
and  be  cured  by  means  of  orange  juice.  "We  have  met 
with  eight  cases  of  eczema  in  infantile  scurvy,  which,  in 
almost  every  instance,  have  yielded  promptly  to  an  anti- 
scorbutic, thus  proving  their  scorbutic  nature.  A  case 
of  this  kind  is  the  following: 

M.  L.,  seven  months  old,  was  getting  "Molkenadap- 
tierte"  milk,  and  in  addition  autolyzed  yeast.  On  May 
25th  it  developed  nasal  diphtheria,  but  soon  afterward 
did  well.  On  June  9th  it  was  gaining,  but  its  pulse  was  160 
and  respirations  80.  A  few  days  later  it  developed 
marked  eczema  about  the  neck  and  to  a  less  extent  on 
the  back  and  buttocks.  The  "capillary  resistance  test" 
was  negative.  Cardiography  tracings  showed  merely  a 
simple  tachycardia.  A  few  days  later  petechial  spots 
appeared  at  the  site  of  the  eczema.  On  June  17th  orange 
juice  was  given.  The  appetite  improved,  the  cardio- 
respiratory syndrome  disappeared,  and  the  child  began  to 
gain.  The  eczema  also  cleared  up  rapidly  without  any 
local  treatment. 

We  wish  to  draw  particular  attention  to  this  skin  con- 
dition, as  it  is  generally  not  mentioned,  or  has  been  re- 
garded merely  as  a  chance  occurrence.  The  report  of  the 
American  Pediatric  Society  includes  two  cases  of  eczema 
as  a  complicating  condition.  This  symptom  is  of  special 
interest  in  view  of  the  fact  that  a  similar  skin  lesion 
constitutes  one  of  the  typical  signs  of  pellagra.  In  a 
case  of  infantile  scurvy  we  have  seen  an  eruption  at  the 
nape  of  the  neck  which  was  symmetrical  and  greatly  re- 
sembled that  of  pellagra.  Andrews  refers  to  the  occur- 
rence of  eczema  in  his  description  of  infantile  beriberi. 

In  a  paper  published  a  few  years  ago  attention  was 


196  SCURVY:    PAST  AND  PRESENT 

drawn  by  Hess  and  Fish  to  the  fact  that  infantile  scurvy 
frequently  is  associated  with  the  exudative  diathesis  of 
Czerny,  a  pathological  condition  which  predisposes  to  the 
development  of  exudations  of  the  skin  and  the  mucous 
membranes.  Infants  suffering  from  this  condition — inter- 
trigo, eczema,  recurrent  bronchitis — seem  to  be  particu- 
larly susceptible  to  scurvy  and  to  develop  it  more  quickly 
than  others. 

As  is  well  known,  edema  constitutes  a  not  infrequent 
symptom  of  adult  scurvy.  It  has  not,  however,  been  ac- 
corded any  place  in  the  symptomatology  of  infantile 
scurvy.  We  do  not  refer  to  the  edema  in  connection  with 
subperiosteal  hemorrhage  or  separation  of  the  epiphyses 
of  the  long  bones,  but  a  mild  and  peculiar  form  which  is 
seen  early  in  the  disease.  It  involves  most  regularly 
the  upper  eyelids,  and  the  legs — especially  the  skin  cover- 
ing the  lower  part  of  the  tibia?.  In  the  latter  site  it  differs 
from  edema  as  usually  encountered,  in  that  it  does  not 
pit  on  pressure ;  it  is  firm,  tense,  causing  some  glossiness 
of  the  overlying  skin,  which  is  rendered  difficult  to  wrinkle 
or  to  pinch  between  the  fingers.  Not  infrequently  the  skin 
is  slightly  reddened,  a  sign  of  interest,  in  view  of  a  similar, 
although  much  more  intense,  hyperemia  seen  in  pellegra. 

In  addition  to  this  very  mild  edema  there  may  be 
marked  swelling,  resulting  in  what  might  be  called,  follow- 
ing the  terminology  of  beriberi,  "wet  scurvy.' '  The  legs, 
body  and  even  the  face  may  be  swollen.  This  has  been 
frequently  described  in  adult  scurvy,  and  occasionally  in 
infantile  scurvy.  The  first  case  of  infantile  scurvy  de- 
scribed in  America,  that  of  Northrup,  had  marked  edema 
of  the  scrotum.  Edema  is  frequently  met  with  in  "ship 
beriberi,"  a  disorder  considered  by  some  writers  to  be  a 
combination  of  beriberi  and  scurvy. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  197 

The  symptom  leading  to  the  diagnosis  of  scurvy  most 
often  is  tenderness  or  swelling  of  one  of  the  extremities, 
as  the  antecedent  clinical  signs,  comprising  latent  scurvy, 
are  generally  overlooked.  These  manifestations  involve 
usually  the  distal  end  of  the  thigh  or  thighs.  The  ten- 
derness is  elicited  most  readily  by  pressure  just  above  the 
knee,  which  causes  the  baby  to  wince,  and  to  quickly  flex 
the  thigh,  a  reaction  termed  by  Heubner  "the  jumping- 
jack  phenomenon."  As  a  result  of  pain  and  tenderness, 
the  leg  lies  often  immobile  in  a  state  of  pseudo-paralysis 
(Fig.  18).  There  may  be  tenderness  elsewhere  than  in 
the  long  bones.  Kerley  refers  to  two  cases  showing  tender- 
ness of  the  spine,  and  we  have  seen  a  similar  case.  Not 
infrequently  there  is  tenderness  of  the  chest  wall,  the 
earliest  symptom  noted  by  nurse  or  mother  being  unac- 
countable crying  whenever  the  baby  is  lifted  by  the  thorax. 
This  is  largely  due  to  the  sensitiveness  of  the  ends  of  the 
cartilage  and  bone  which  are  pressed  together  at 
their  junction. 

An  early  sign  of  infantile  scurvy  is  beading  of  the  ribs 
— the  development  of  a  "rosary"  similar  to  that  charac- 
teristic of  rickets  (Fig.  19).  This  has  recently  been  de- 
scribed by  Hess  and  Unger  in  an  article  devoted  to  this 
subject.  That  this  rosary  is  truly  scorbutic  and  not  rha- 
chitic  is  proved  by  the  fact  that  it  recedes  rapidly  when 
antiscorbutic  foodstuff  is  given,  and  that  it  remains  unin- 
fluenced by  treatment  with  cod  liver  oil.  A  similar  scor- 
butic rosary  occurs  in  guinea-pig  scurvy,  but  has  been 
termed  "pseudo-rhachitic."  It  is  important  that  this 
sign  should  be  recognized,  as  it  is  probable  that  much  of 
the  confusion  regarding  the  relationship  and  frequent 
association  of  these  two  diseases  is  due  to  considering 
the  beading  rhachitic.     The  interpretation  of  infantile 


198  SCURVY:    PAST  AND  PRESENT 

scurry  as  "acute  rickets,"  the  view  held  previous  to  the 
writings  of  Barlow,  was  based  largely  on  the  develop- 
ment of  the  rosary.  To-day  the  error  is  made  of  regard- 
ing early  scurvy  as  chronic  rickets ;  the  rickets  supposed 
to  be  occasioned  by  a  diet  of  condensed  milk  is  probably 
more  often  scurvy.  This  beading  differs  generally  from 
the  round  knobby  "  rosary "  usually  encountered.  It  is 
more  angular,  the  junction  taking  on  a  step-like  form,  as 
if  the  abutting  ends  of  the  cartilage  and  the  bone  were  of 
unequal  size,  and  not  well  fitted  to  each  other.  In  the 
accompanying  radiograph  (Fig.  19)  it  will  be  noted  that 
the  ' '  beads  "  present  an  irregular  appearance. 

In  Figs.  6, 16  and  17  will  be  seen  illustrations  of  a  sep- 
aration of  the  epiphyses  of  the  head  of  the  humerus,  and 
of  partial  and  of  complete  separation  of  the  lower  ends  of 
the  femora.  This  is  a  frequent  lesion  of  fully-developed 
scurvy  in  infants,  children,  and  even  in  young  adults.  It 
is  most  frequent  at  the  lower  end  of  the  femur,  the  upper 
end  of  the  tibia,  the  head  of  the  humerus,  and  the  costo- 
chondral  junctions.  It  is  to  these  epiphyseal  separations 
that  the  term  fracture  or  infraction  usually  refers.  Union 
is  remarkably  perfect  even  where  no  splint  has  been  em- 
ployed, and  nature  has  effected  the  cure  (Fig.  7).  Occa- 
sionally there  is  some  deformity,  as  when  coxa  vara 
develops.  The  callus  is  often  remarkably  large;  an  old 
callus  sometimes  undergoes  destruction  in  the  course 
of  scurvy. 

We  have  referred  to  use  of  rontgenograms  in  connec- 
tion with  separation  of  the  epiphyses,  subperiosteal 
hemorrhage,  cardiac  enlargement  and  beading  of  the  ribs. 
In  addition  to  its  application  in  these  connections,  the 
X-ray  may  be  of  service  to  show  a  peculiar  alteration  of 
the  ends  of  the  long  bones — the  white  line  of  Fraenkel. 


Fig.    Is. — Infant  with  marked  scurvy.     Characteristic  posture  and  swelling  of  right  thigh. 


Fig.   19. — Same  infant  as  in  figure  17.     Scorbutic  beading  of  the  ribs  (rosary).     This  devel- 
oped on  a  diet  which  included  cod  liver  oil,  and  decreased  when  an  antiscorbutic  was  given. 
Note  peculiar  ragged  appearance  of  "beads." 


Fig.  20      Radiograph.      Infant    n    months  of  age,  Bhowing   "whiU    line"   at    wrist    some 

months  after  cure  of  .scurvy. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  199 

This  is  portrayed  in  Fig.  20.  It  is  best  seen  at  the  lower 
ends  of  the  radius  and  femur,  and  appears  as  a  white, 
transverse,  somewhat  irregular  band.  Its  diagnostic 
value  has  been  greatly  exaggerated,  as  it  is  frequently  not 
present  when  the  disease  is  advanced  (observe  radio- 
graphs illustrating  separation  of  the  epiphyses).  This 
sign  should  therefore  not  be  relied  on  for  establishing  the 
diagnosis.  Furthermore,  changes  may  be  seen  in  connec- 
tion with  rickets  (cases  receiving  antiscorbutic  diet) 
which  are  very  difficult  to  differentiate  from  the  "white 
line."  It  cannot  be  employed  as  a  criterion  of  the  prog- 
ress of  the  case,  as  it  may  persist  for  months  after  all 
other  signs  and  symptoms  have  disappeared. 

The  joints  may  be  involved  in  scurvy.  In  most  in- 
stances, however,  where  swelling  of  the  joints  is  diag- 
nosed, the  lesion  is  periarticular.  An  effusion  of  serum 
or  of  blood  does  occur  occasionally  into  the  joints  and 
has  been  found  at  operation,  at  necropsy,  and  by  puncture. 
If  these  effusions  are  allowed  to  go  undisturbed,  to  be 
absorbed  as  a  result  of  antiscorbutic  treatment,  they 
rarely  suppurate.  Czerny  and  Keller  report  the  articular 
fluid  as  invariably  sterile. 

The  cardiovascular  system  has  been  given  but  scant 
attention  in  connection  with  scurvy.  Adults  complain  not 
infrequently  of  palpitation  and  pain  over  the  pericar- 
dium, or  rather  of  a  tightness  or  oppression  in  the  chest. 
Little  information  is  given  regarding  the  size  of  the 
heart.  Darling  described  enlargement  of  the  heart,  espe- 
cially a  right-sided  hypertrophy,  which  he  thought  was 
pathognomonic  of  the  Rand  type  of  scurvy.  The  pulse  is 
described  in  some  cases  as  slow,  and  in  others  as  rapid. 
In  descriptions  of  infantile  scurvy  the  entire  subject  is 
generally  passed  over  without  mention — for  example,  in 


200  SCURVY:    PAST  AND  PRESENT 

the  excellent  report  of  the  American  Pediatric  Society 
nothing  whatsoever  is  stated  regarding  the  heart's 
action  or  the  pulse.  Barlow  wrote :  "  There  is  nothing  to 
note  regarding  the  heart  and  lungs." 

In  a  paper  written  a  few  years  ago,  it  was  pointed 
out  by  the  author  that  there  is  frequently  enlargement  of 
the  heart,  and  more  especially  of  the  right  heart.  This 
can  be  elicited  at  the  bedside  and  has  been  substantiated 
in  numerous  cases  by  means  of  the  Rontgen-ray,  which 
demonstrates  not  only  enlargement  of  the  heart,  but  also 
a  marked  broadening  at  its  base,  at  the  site  of  the  large 
vessels  (Fig.  21).  These  phenomena  resemble  closely  the 
description  of  Reinhard  in  cases  of  beriberi. 

Necropsy  protocols  usually  are  incomplete  and  un- 
satisfactory in  their  descriptions  of  the  heart.  The  ex- 
cellent monograph  of  Schoedel  and  Nauwerk,  however, 
which  reports  five  careful  necropsies,  contains  the  follow- 
ing data  regarding  three : 

1.  Pericardial  fluid  somewhat  increased,  both  ven- 
tricles moderately  dilated,  the  right  somewhat  hyper- 
trophic. 

2.  The  heart  showed  a  hypertrophy  of  the  right  and 
left  ventricles,  as  well  as  dilatation  of  the  right  ventricle. 

3.  The  right  ventricle  dilated  and  slightly  hypertro- 
phied,  the  muscles  pale  and  tough. 

In  addition  to  this  enlargement  of  the  heart,  or  per- 
haps associated  with  it,  there  is  a  combination  of  signs 
which  has  been  termed  "the  cardiorespiratory  syn- 
drome" (Hess).  It  will  be  noted  in  the  above  description 
of  a  case  of  subacute  scurvy,  that  the  pulse-  or  heart-beat 
was  frequently  over  150,  and  the  respiration  60.  These 
phenomena  were  noted  in  several  instances  before  their 
significance  and  intimate  relationship  to  scurvy  were  rea- 


9- 
o' 


V 
- 


-3 


SYMPTOMATOLOGY  AND  DIAGNOSIS  201 

lized.  The  heart-beat  not  infrequently  is  found  to  be  200 
per  minute,  and  to  be  characterized  by  marked  lability — 
increasing  to  an  astonishing  degree  as  the  result  of  slight 
exertion  or  excitement.  A  mild  febrile  disturbance  caus- 
ing a  rise  of  temperature  to  little  more  than  100°  F.  will 
send  the  pulse-rate  up  30  beats.  It  must  not  be  thought 
that  this  refers  to  severe  cases ;  the  babies  we  have  in  mind 
are  similar  to  the  one  cited  as  an  instance  of  subacute 
scurvy.  Apparently  they  are  not  ill,  but  show  merely 
some  tenderness  of  the  thighs,  pallor,  and  the  other  minor 
signs  described.  The  cardiographic  tracings  showed  a 
simple  tachycardia  with  an  exceptionally  tall  T-wave  in 
some  tracings,  such  as  is  commonly  seen  in  exophthalmic 
goitre  (Fig.  22). 

The  rapidity  of  respirations  is  perhaps  a  more  delicate 
indicator  of  this  disturbance  than  the  pulse  and  has  been 
found  to  be  markedly  affected  when  the  latter  was  merely 
slightly  increased  in  rate.  For  example,  in  one  instance 
the  respirations  were  64,  60  and  64  on  three  successive 
days,  while  the  pulse  was  124, 141  and  136 ;  in  other  words, 
there  was  a  2 : 1  instead  of  the  normal  4 : 1  pulse-respira- 
tion ratio.  The  accompanying  chart  (Fig.  15)  illustrates 
the  phenomenon  in  all  its  details  better  than  a  verbal 
description.  There  is  one  point  in  connection  with  it, 
to  which  especial  attention  should  be  called.  This  is  a 
reaction  evident  at  a  glance  at  the  chart — the  sharp  drop 
in  the  pulse  and  in  the  respiratory  rate  when  orange  juice 
was  given.  It  is  the  essence  of  the  phenomenon ;  a  thera- 
peutic response  which  proves  that  the  rapidity  is  scor- 
butic in  nature. 

The  main  involvement  of  the  respiratory  system  in 
scurvy  is  the  polypncea  just  described  in  connection  with 
the  cardiorespiratory  syndrome.     There  is  no  aphonia, 


202  SCURVY:    PAST  AND  PRESENT 

a  sign  so  typical  of  adult  and  of  infantile  beriberi,  al- 
though at  times  the  voice  is  abnormal  and  whining.  The 
lungs  frequently  show  some  dullness  posteriorly,  which 
may  be  due  to  engorgement  or  to  the  pressure  of  the 
enlarged  heart.  Pneumonia  is  a  frequent  complication 
and  edema  a  terminal  event.  Hydrothorax  associated 
with  hydropericardium  is  of  frequent  occurrence,  and  was 
noted  in  the  early  description  of  this  disease  in  adults 
and  in  the  first  account  of  Barlow.  These  effusions  rarely 
progress  to  what  may  be  termed  the  clinical  degree  and 
under  antiscorbutic  treatment  are  rapidly  absorbed. 

It  is  commonly  thought  that  scurvy  does  not  involve 
the  nervous  system;  that  this  is  a  feature  which  distin- 
guishes it  sharply  from  beriberi,  another  "deficiency 
disease."  This  view  is  incorrect,  for  the  nervous  system 
is  probably  affected  in  many  cases  of  scurvy.  The  rapid- 
ity and  lability  of  the  pulse,  combined  with  the  rapid 
respirations,  would  seem  to  be  due  to  a  disturbance  of  the 
vagus  mechanism.  It  is  true  that  in  beriberi  the  vagus  is 
involved  to  a  still  greater  extent,  especially  its  recurrent 
laryngeal  branch  which  brings  about  the  characteristic 
aphonia.  In  scurvy  the  knee-reflexes  are  generally  in- 
creased. Very  rarely  they  are  absent  in  infantile  scurvy, 
as  described  in  adults.  It  is  impossible  to  judge  whether 
the  pain  and  tenderness  in  infants  are  due  in  part  to  a 
sensitiveness  of  the  nerve  trunks  as  well  as  of  the  perios- 
teum. Careful  studies  in  adult  scurvy  should  furnish  an 
answer  to  this  question.  No  methodical  examination  for 
areas  of  anaesthesia  or  paresthesia,  signs  which  occur  so 
frequently  in  connection  with  beriberi,  has  been  carried 
out  in  scurvy.  In  certain  epidemics,  however,  pains  in  the 
limbs  have  been  prominent  symptoms. 

The  optic  discs  are  generally  pale  in  both  infants  and 


SYMPTOMATOLOGY  AND  DIAGNOSIS  203 

in  adults,  with  occasional  signs  of  neuroedema.  Nycta- 
lopia, so  frequently  encountered,  must  be  regarded  as  a 
circulatory  symptom  rather  than  as  one  of  nervous  origin. 

In  a  recent  paper  the  author  described  a  focal  degener- 
ation of  the  lumbar  cord  in  a  case  of  infantile  scurvy, 
the  lesion  involving  mainly  the  anterior  horn  cells  (Figs. 
3  and  4).  In  view  of  this  report  it  would  be  well  to 
watch  for  corresponding  clinical  signs  of  involvement 
of  the  spinal  cord.  Herpes  has  been  described  in  connec- 
tion with  both  adult  and  infantile  scurvy.  In  one  of  the 
early  cases  in  the  American  literature  Fruitnight  reported 
a  case  with  herpes  in  a  girl  five  years  of  age.  In  con- 
sidering the  role  of  the  nervous  system,  mention  should 
be  made  of  cases  where  sweating  constituted  an  important 
symptom.  Finkelstein  lays  particular  stress  on  this 
symptom  in  infantile  scurvy.  We  have  not  met  with  it 
frequently;  possibly  it  is  due  in  part  to  complicat- 
ing rickets. 

As  would  be  expected,  the  nervous  system  is  at  times 
the  site  of  hemorrhage.  Such  lesions  cannot,  however, 
be  considered  essentially  nervous.  For  instance,  hemor- 
rhage into  the  meninges  may  occur,  as  in  the  case  of 
Sammis,  where  there  was  "a  general  clonic  convulsion" 
before  death,  and  a  blood-clot  2y2  inches  long  by  y2  inch 
wide  was  found  at  necropsy  between  the  dura  and  arach- 
noid. Fife  reported  a  similar  case.  Finkelstein  also  has 
drawn  attention  to  the  occurrence  of  meningeal  hemor- 
rhage, and  Hess  and  Fish  reported  obtaining  bloody  cere- 
brospinal fluid  from  a  case  with  meningeal  symptoms. 
Recently  Aschoff  and  Koch  have  depicted  hemorrhages  in 
the  sheath  of  the  sciatic  nerve,  which  undoubtedly  must 
have  given  rise  to  symptoms  during  life. 

In  view  of  many  of  these  symptoms,  especially  those 


204  SCURVY:    PAST  AND  PRESENT 

involving  the  vagus,  scurvy  must  be  looked  upon  as  a  dis- 
order which  may  seriously  affect  the  nervous  system. 
Furthermore,  when  we  note  the  marked  reaction  brought 
about  by  the  antiscorbutic  vitamine — for  example,  the 
sharp  fall  in  the  rate  of  respirations  and  of  pulse,  as 
shown  in  Fig.  15,  after  giving  orange  juice,  we  must  con- 
clude that  the  antiscorbutic  vitamine  functions,  at  least 
indirectly  as  an  antineuritic  vitamine — that  it  must  pos- 
sess this  character  to  allay  the  various  nervous  signs  of 
this  disorder. 

The  urinary  system  is  frequently  involved  in  the  course 
of  scurvy.  Among  38  cases  Still  reports  that  89  per  cent, 
gave  evidence  of  urinary  changes  and  that  60  per  cent, 
showed  hematuria.  Finkelstein  found  urinary  signs  in 
at  least  a  third  of  his  cases.  Our  figures,  the  result  of  a 
study  of  subacute  and  mildly  acute  cases,  correspond 
more  nearly  with  those  of  Finkelstein. 

The  occurrence  of  pronounced  renal  hemorrhage  as  a 
first  symptom  of  scurvy  is  emphasized  in  many  descrip- 
tions of  this  disease,  and  has  impressed  itself  in  the  minds 
of  physicians.  It  is  true  that  this  occurs  sometimes  at 
the  onset,  as  does  hemorrhage  into  or  about  the  joints,  or 
hemorrhage  behind  the  eyeball.  It  is  well  to  bear  these 
possibilities  in  mind,  but  they  must  be  regarded  as  very 
exceptional  early  signs  of  this  disorder.  We  have  en- 
countered frank  hematuria  but  once  in  the  early  stage  of 
infantile  scurvy.  The  blood  emanates  generally  from  the 
kidneys,  although  the  submucous  hemorrhages  of  the 
bladder  as  well  as  in  the  urethra,  described  both  in  man 
and  in  guinea-pigs,  indicate  that  the  blood  in  the  urine 
may  have  its  origin  lower  down  in  the  tract.  This  bleed- 
ing should  be  regarded  not  as  a  sign  of  nephritis,  but 
rather  as  a  hemorrhagic  manifestation.     It  is  less  fre- 


SYMPTOMATOLOGY  AND  DIAGNOSIS  205 

quent  in  adults  than  in  infants.  O'Shea  reports  some  de- 
gree of  hemorrhage  in  15  per  cent,  of  his  cases  (adults). 

A  true  nephritis,  however,  may  occur  in  connection 
with  scurvy.  There  may  be  albumen  and  many  casts,  or  a 
urine  loaded  with  casts  and  cylindroids.  These  peculiar 
casts  may  appear  suddenly,  as  in  the  alimentary  intoxi- 
cation of  infants,  and  disappear  just  as  rapidly  when 
antiscorbutic  treatment  is  given.  The  urine  may  contain 
a  large  number  of  pus  cells  as  in  pyelitis.  This  condition 
may  be  accompanied  by  irregular  fever,  but  in  two  in- 
stances we  have  encountered  it  where  the  temperature 
was  normal.  It  is  to  be  regarded,  probably,  merely  as  one 
of  the  manifestations  of  secondary  infection  so  com- 
monly associated  with  scurvy.  Some  pus  cells  may  con- 
tinue to  be  present  in  the  urine  for  a  period  of  months. 
This  is  likewise  true  of  the  red  cells.  We  have  under 
observation  at  present  an  infant  which  had  subacute 
scurvy  almost  three  years  ago  and  still  has  red  blood- 
cells  in  the  urine. 

Oliguria  is  a  common  symptom  of  both  adult  and  in- 
fantile scurvy.  Lind  mentioned  this  symptom,  and  in  this 
connection  remarks  on  the  beneficent  effect  of  antiscor- 
butic treatment.  Charpentier  called  attention  to  the  fact 
that  in  a  case  of  scurvy  the  urine  decreased  from  1250  g. 
to  800  g.  The  report  of  the  American  Pediatric  Society 
mentions  scanty  urine  in  9  cases  and  suppression  of  urine 
in  one.  This  sign,  however,  was  not  emphasized  until 
recently,  when  Gerstenberger,  and  Hess  and  Unger  drew 
attention  to  its  frequent  occurrence  in  infants.  It  has 
some  diagnostic  significance  and  should  be  borne  in  mind 
where  a  decreased  excretion  of  urine  is  reported.  A 
counterpart  of  this  symptom  is  the  sudden  outpouring 
of  urine  frequently  noted  after  antiscorbutic  treatment 


206 


SCURVY:    PAST  AND  PRESENT 


has  been  instituted.  This  polyuria  accounts  for  the  loss 
of  weight  or  lack  of  gain  which  sometimes  accompanies 
unmistakable  general  improvement,  and  which  is  difficult 
otherwise  to  understand  (Fig.  23).  It  is  interesting  to 
learn  that  oliguria  occurs  commonly  in  both  adult  and 
infantile  beriberi. 

One  of  the  earliest,  as  well  as  one  of  the  most  constant 
symptoms  of  scurvy,  is  a  lack  of  appetite.    It  is  a  typical 


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Fig.  23. — Joseph  G.,   aged  9  months.     Chart  showing  stationary  weight   (due  to   oliguria 

followed  by  diuresis)  in  spite  of  marked  variation  of  fluid  intake.     A=Schloss  milk;  B=cod 

liver  oil;  C=egg  yolk;  D=l  ounce  of  orange  juice;  E=potato  (orange  juice  stopped). 

sign  of  latent  scurvy,  although  occasionally  we  have  met 
with  cases  where  the  appetite  remained  unimpaired  until 
the  hemorrhagic  stage  was  reached.  In  adults  there  is 
sometimes  bulimia  and  a  marked  capriciousness  of  the 
appetite.  Anorexia  is  a  true  scorbutic  symptom,  disap- 
pearing with  remarkable  rapidity  when  antiscorbutic  food 
is  given,  and  not  capable  of  alleviation  by  tincture  of 
genitian  or  other  vegetable  bitters.  Whether  it  depends 
upon  a  lack  of  secretions  in  the  gastro-intestinal  tract 


SYMPTOMATOLOGY  AND  DIAGNOSIS  207 

is  not  known,  as  there  has  been  no  thorough  study  of  this 
aspect  of  the  disorder.  The  hydrochloric  acid  generally 
is  deficient  in  cases  of  scurvy.  Recently  McCarrison  has 
laid  emphasis  on  the  importance  of  the  impairment  of 
the  digestion  and  assimilative  function  in  scurvy.  This 
subject  gains  added  interest  in  view  of  the  recent  reports 
of  Uhlmann  as  well  as  of  Voegtlin,  showing  that  water- 
soluble  vitamine  acts  as  a  stimulant  for  the  various  secre- 
tions of  the  gastro-intestinal  tract. 

As  a  result  of  McCollum's  statement  that  scurvy  is 
due  mainly  to  constipation,  marked  attention  has  been 
directed  recently  to  the  action  of  the  bowels  in  this  dis- 
order. This  question  has  been  discussed  in  the  chapter 
on  etiology,  and,  therefore,  will  be  referred  to  in  this 
place  merely  from  the  clinical  viewpoint.  In  our  experi- 
ence the  activity  of  the  bowel  varies  greatly  in  cases  of 
latent  or  subacute  scurvy.  In  a  great  many  instances  it 
has  been  normal ;  more  often  there  has  been  slight  consti- 
pation, and  exceptionally  there  has  been  irregular  diar- 
rhoea. In  other  words,  no  causative  relationship  or  paral- 
lelism could  be  observed  between  the  emptying  of  the 
intestinal  tract  and  the  development  of  scurvy.  This  in 
general  has  been  the  experience  of  others.  In  the  report 
of  the  American  Pediatric  Society  the  bowels  are  stated 
as  having  been  regular  in  74  cases,  irregular  in  15,  con- 
stipated in  126,  and  diarrhoeal  in  65.  It  may  be  added 
that  we  were  unable  to  cure  scurvy  by  means  of  liquid 
petrolatum  or  phenolphthalein,  either  in  infants  or  in 
guinea-pigs,  and  likewise  unable  to  protect  guinea-pigs 
from  scurvy  by  means  of  various  laxatives.  On  the  other 
hand,  opium  given  in  the  form  of  the  camphorated  tinc- 
ture did  not  lead  to  an  intensification  of  the  symptoms, 


208  SCURVY:    PAST  AND  PRESENT 

although,  in  one  case,  the  bowels  did  not  move  for  over 
three  days. 

As  complications  involving  the  gastro-intestinal  tract 
may  be  mentioned  the  vomiting  of  blood,  which  is  stated 
in  the  above  report  as  occnrring  in  2  of  the  361  cases, 
as  well  as  bleeding  from  the  bowel,  which  was  noted  in 
37  cases,  in  12  of  which  there  was  bloody  diarrhoea.  How- 
ever, these  are  late  symptoms,  and  correspond  to  the  my- 
cotic ulcers  which  are  so  frequently  found,  especially  in 
the  large  intestine,  in  cases  of  scurvy.  Mention  may 
again  be  made  of  the  fact  that  hemorrhages  may  occur 
under  the  peritoneum  and  give  rise  to  symptoms  simulat- 
ing appendicitis  or  general  peritonitis. 

Jaundice  has  been  described  in  connection  with  certain 
epidemics  of  scurvy.  To  our  knowledge  it  has  not  been 
reported  in  infants. 

The  presence  of  worms  has  been  frequently  reported 
in  the  bowel  or  in  the  stool  of  patients  suffering  from 
beriberi.  There  have  been  no  similar  investigations  in 
relation  to  scurvy.  It  would  be  interesting  to  inquire  into 
this  question,  as  it  is  quite  possible  that  a  lack  of  anti- 
scorbutic foodstuff  may  favor  the  presence  of  parasites  in 
the  intestinal  canal. 

Before  closing  this  consideration  of  the  involvement 
of  the  alimentary  tract,  we  would  call  attention  to  the 
relation  of  stomatitis  to  scurvy.  Among  adults  this  is 
a  common  complication.  In  infants  it  is  uncommon,  due 
to  the  absence  of  carious  teeth  and  secondary  infection; 
we  have  encountered  it  in  but  two  instances.  Stomatitis 
is  of  importance  in  this  connection,  as  it  frequently  de- 
velops  on  the  basis  of  malnutrition,  scurvy  being  one  of 
the  disorders  which  may  constitute  the  substratum.  Such 
may  be  the  case  where  stomatitis  occurs  in  epidemic  form 


SYMPTOMATOLOGY  AND  DIAGNOSIS 


209 


— for  example,  among  large  bodies  of  troops.  It  may  be 
remarked  that  stomatitis  at  times  was  a  very  common 
disease  among  the  soldiers  in  the  recent  war. 

TABLE  4 
The  Platelets  and  Other  Blood-Cells  in  Scurvy 


Name 

Date 

Platelets 

Leuko- 

Erythro- 

Hmgl. % 

cytes 

cytes 

(Sahli) 

M.  H. 

5/  3 
5/  4 
5/  5 

5/  8 
5/16 

280,000 
248,000 

10,000 
15,900 

4,300,000 

35 

Boiled  orange  juice 
given. 

7/    2 

6,800 

5,456,000 

40 

Well  but  pale. 

A.  L. 

5/  3 
5/  5 
5/  9 
S/il 
5/13 
5/i6 

300,000 
382,000 

21,000 
11,500 

5,480,000 

65 

H.  C. 

5/  8 
5/  9 
5/13 
5/l6 

320,000 
362,000 

20,000 

5,340,000 

70 

B.  B. 

5/  4 

496,000 

21,000 

A  severe  case. 

5/13 

585,000 

14,000 

3,200,000 

70 

5/i8 

17,600 

7/i3 

40,000 

7,672,000 

82 

Has    gained    well 
lately. 

7/15 

7,640,000 

88 

H.  Y. 

5/15 
S/16 
7/  9 

560,000 
424,000 

5,750,000 

45 

Scurvy  is  associated  with  an  alteration  of  both  the 
blood  and  the  blood-vessels.  The  characteristic  pallor, 
which  is  one  of  the  most  common  as  well  as  earliest  symp- 
toms, is  due  in  a  large  measure  to  the  anemia.  This 
anemia  is  of  the  secondary  type,  but  has  definite  pecu- 
liarities, and  does  not  resemble  that  encountered  in  the 
course  of  tuberculosis,  rickets  or  marasmus.  The  hemo- 
globin is  greatly  diminished,  far  out  of  proportion  to  the 
decrease  in  the  number  of  the  red  cells.  Not  infrequently 
we  will  find  a  hemoglobin  index  of  0.5.  Table  4,  above 
taken  from  the  article  on  this  subject  by  Hess  and 
Fish    (1914),    brings    out    the    details    of    the    blood- 

14 


210  SCURVY:    PAST  AND  PRESENT 

picture.  It  shows  that  there  may  be  a  polycythe- 
mia, which  may  persist  after  the  other  signs  of  the 
disorder  have  disappeared.  Brandt  has  recently  made 
similar  observations,  reporting  in  one  instance  over  ten 
million  red  cells  two  months  after  treatment.  In  soldiers 
suffering  from  scurvy  Wassermann  has  encountered  cases 
where,  during  convalescence,  the  red-cell  count  has  risen 
to  over  six  or  seven  millions  and  the  hemoglobin  to  110  or 
120  per  cent.  Under  the  microscope  the  red  cells  show 
poikilocytosis,  anisocytosis  and  a  lack  of  hemoglobin; 
they  are  slightly  enlarged,  with  the  occasional  occurrence 
of  exceptionally  large  cells  resembling  the  "dropsical 
cells' '  described  in  connection  with  chlorosis.  Sometimes 
a  few  nucleated  red  cells  and  myeloblasts  are  seen; 
megaloblasts  are  also  reported.3  The  blood-picture  bears 
a  remarkable  similarity  to  that  of  chlorosis,  a  point  of 
interest,  in  view  of  the  fact  that  both  scurvy  and  chlo- 
rosis have  been  attributed  to  a  disordered  function  of  the 
endocrine  glands.  The  " dropsical  cells' >  suggest  a  dis- 
turbance of  the  salt  balance  in  the  plasma.  In  some  cases 
we  have  found  a  decreased  fragility  of  the  red  cells,  which 
also  has  been  described  in  chlorosis. 

The  total  number  of  leucocytes  is  slightly  increased. 
In  our  cases  the  mononuclear  cells  have  averaged  66  per 
cent.,  which  is  somewhat  high  even  for  infants.  This  has 
been  the  experience  of  Labor,  who,  however,  also  describes 
an  eosinoimilia  during  convalescence,  a  phenomenon  which 
we  have  not  encountered.  Some  describe  a  marked  in- 
crease in  the  polynuclear  cells,  which,  probably,  is  to  be 


3  Senator  regarded  the  marrow  in  scurvy  as  being  aplastic.  Nobecourt, 
Tixier  and  Maillet  report  post-mortem  examinations  where  the  marrow 
showed  an  increased  number  of  myelocytes  and  nucleated  red  cells  of  various 
kinds.  They  consider  the  typical  blood  change  an  intense  myeloid  reaction 
of  the  blood. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  211 

regarded  as  the  reaction  to  secondary  infections.  There 
is  indeed  a  marked  difference  of  opinion  in  regard  to  the 
morphology  of  the  blood  in  scurvy  in  adults  as  well  as 
in  infants.  Some  found  a  large  number  of  one  type  of 
cell — for  example,  nucleated  red  cells,  myelocytes,  eosino- 
philes — whereas  others  have  failed  to  observe  an  increase 
of  these  cells.  The  divergent  reports  probably  should  be 
attributed  to  the  fact  that  the  investigators  are  describ- 
ing scurvy  of  various  grades  of  severity,  of  different 
stages  of  development,  or  complicated  by  intercur- 
rent disease. 

Nobecourt,  Tixier,  and  Maillet  have  questioned 
whether  there  is  always  complete  recovery  from  this 
anemia,  which  is  severe  from  the  standpoint  of  hemoglo- 
bin and  iron.  The  older  authors  reported  instances  where 
men  have  been  weakly  and  ailing  for  the  remainder  of 
their  lives  after  an  attack  of  scurvy.  In  some  infants 
pallor  and  anemia  may  persist  for  months  after  appar- 
ent cure;  however,  this  is  the  exception  rather  than 
the  rule. 

In  view  of  the  fact  that  scurvy  frequently  is  classed 
as  a  hemorrhagic  disease,  and  that  hemorrhages  play  such 
an  important  role  in  its  symptomatology,  a  consideration 
of  the  factors  concerned  in  the  coagulability  of  the  blood 
is  of  interest.  In  an  investigation  (Hess  and  Fish)  it 
was  found  that  the  oxalated  plasma  (of  blood  taken  di- 
rectly from  a  vein)  showed  a  slightly  delayed  coagulation 
time — eight  to  fourteen  minutes.  The  "bleeding  time" 
carried  out  according  to  the  simple  method  of  Duke  was 
slightly  increased.  Holt  reports  a  case  where  a  child 
bled  to  death  following  incision  into  an  epiphyseal  swelling 
at  the  lower  end  of  the  femur.  The  number  of  blood 
platelets  is  increased,  running  parallel,  as  is  usually  the 


212  SCURVY:    PAST  AND  PRESENT 

case,  with  the  number  of  red  cells  (Table  4) .  This  increase 
in  the  blood-platelets,  recently  confirmed  by  Tobler  and 
by  Brandt,  is  a  very  exceptional  phenomenon,  and  was  not 
anticipated  in  connection  with  a  disorder  characterized 
by  hemorrhage.  The  antithrombin  content  of  the  plasma 
is  normal. 

The  investigation  was  directed  to  a  study  of  the  integ- 
rity of  the  blood-vessels  in  order  to  account  for  the  hemor- 
rhages. To  this  end  the  "capillary  resistance  test"  was 
devised.4  In  the  majority  of  cases  this  was  found  to  be 
"positive"  (the  blood-vessels  showing  an  increased  per- 
meability) and  to  become  negative  when  antiscorbutics 
were  given  and  the  symptoms  disappeared.  This  shows 
that  the  cellular  structure  of  the  vessels  is  altered  in  the 
course  of  scurvy,  and  indicates  probably  that  this  is  an 
important  cause  of  the  hemorrhages.  The  edema  of  the 
face  and  ankles,  the  outflow  of  serum  into  the  body  cavi- 
ties and  into  the  muscles  (Barlow)  must  be  regarded  as 
other  evidences  of  the  inadequacy  of  the  vessel  walls. 
The  tendency  of  children  with  exudative  diathesis  to  de- 
velop scurvy  is  perhaps  still  another  manifestation  of 
vascular  weakness.  This  point  of  view  has  been  strength- 
ened recently  by  the  pathological  studies  of  Aschoff  and 
Koch,  who  regard  scurvy  as  a  nutritional  disorder  in 

*  A  blood-pressure  band,  or  tourniquet,  is  placed  about  the  arm,  and 
the  pressure  increased  until  the  forearm  becomes  cyanosed  and  the  radial 
pulse  is  almost  obliterated.  The  pressure  is  then  maintained  at  this  level 
for  3  minutes.  The  principle  of  this  test  consists  in  subjecting  the  capil- 
laries and  venules  to  increased  intra-vascular  pressure  to  observe  whether 
this  strain  results  in  the  escape  of  blood.  In  infants  the  pressure  was 
usually  raised  to  90  mm.;  in  some  cases  it  had  to  be  raised  higher  in  order 
to  entirely   obstruct  the  return   flow  of  the  blood. 

The  test  is  considered  to  be  "positive"  when  the  forearm  shows  many 
petechial  spots.  In  normal  infants  petechias  were  almost  always  absent,  or 
there  were  few  to  be  seen.  This  is  not  a  specific  test  for  scurvy,  but  dem- 
on trates  a  weakness  of  the  vessel  walls,  whatsoever  may  be  the  cause.  It  is 
found  to  be  positive  in  the  majority  of  cases  of  scurvy. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  213 

which  there  is  a  lack  of  some  colloidal  substance  needed 
for  the  normal  structure  of  the  vessels. 

When  one  makes  a  subcutaneous  puncture  in  infants 
suffering  from  scurvy,  a  small  hemorrhage  very  often 
develops  at  the  site  of  the  puncture  wound.  This  is  not 
the  case  when  one  makes  a  hypodermic  puncture  in  a 
normal  person  or  in  a  hemophiliac,  although  it  does 
occur  in  cases  of  purpura.  This  "stick  test'7  is  not  a 
constant  sign  of  scurvy,  but,  like  the  capillary  resistance 
test,  was  found  in  many  cases  and  disappeared  with  the 
subsidence  of  the  disorder.  It  shows  that  the  cells  of  the 
skin  and  subcutaneous  tissues  are  affected,  and  possibly 
that  their  thromboplastic  power  is  diminished. 

Nutrition  and  Growth. — The  general  nutrition  suffers  in 
scurvy  as  the  disease  progresses.  It  is  a  mistake,  how- 
ever, to  picture  the  scorbutic  individual,  either  adult  or 
infant,  as  in  a  state  of  malnutrition.  Not  infrequently 
he  appears  well  nourished,  an  appearance  which  is  height- 
ened by  the  slight  edema  of  the  face.  Infants  generally 
for  a  period  of  weeks  or  months  preceding  the  onset  main- 
tain a  stationary  weight.  This  may  be  the  only  sign  of 
the  scorbutic  condition.    For  example : 

An  infant  seen  in  1915  gained  about  one-half  a  pound 
during  the  months  of  February,  March,  April  and  May. 
At  this  time  it  was  somewhat  over  9  months  of  age  and 
had  never  received  raw  milk  or  other  antiscorbutic  food. 
In  June  it  was  given  orange-peel  juice,  and  gained  2 
pounds  within  a  month.  There  were  no  other  scorbutic 
signs  or  symptoms,  and  no  loss  of  appetite  during  the 
months  of  February  and  March,  although  the  baby  was 
suffering  from  a  progressive  scurvy. 

The  growth  impulse  of  the  body  throughout  an  attack 
of  scurvy  remains  unimpaired,  being  merely  in  an  inactive 


214 


SCURVY:    PAST  AND  PRESENT 


or  quiescent  state.  Fig.  14  shows  this  very  well,  demon- 
strating that  when  an  antiscorbutic  food  is  added  to  the 
dietary  the  gain  may  be  abnormally  great — there  may  be 
supergrowth.  Generally  such  marked  increases  are  due 
to  an  increase  in  the  consumption  of  food,  following  the 
stimulation  of  the  appetite.  However,  decided  gain  in 
weight  may  follow  the  giving  of  orange  juice  or  other 


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Fig.  24. — Development  of  scurvy  in  spite  of  normal  gain  in  weight  in  a  baby  who  had  been 

underfed  since  birth. 

antiscorbutic  despite  the  fact  that  the  intake  of  food  is 
maintained  at  the  same  level. 

Although  it  may  be  stated  as  a  principle  that  the 
development  of  scurvy  is  accompanied  by  a  failure  to 
gain  in  weight,  there  are  exceptions  to  this  rule.  Under 
certain  conditions  the  weight  may  follow  a  perfectly 
normal  course  during  the  entire  period.  Fig.  24  illus- 
trates this  clinical  paradox : 


SYMPTOMATOLOGY  AND  DIAGNOSIS  215 

A  baby  was  seen  in  January,  when  it  was  7y2  months 
of  age.  Toward  the  end  of  February,  in  spite  of  constant 
and  normal  gain  in  weight,  he  manifested  unmistakable 
signs  of  scurvy — peridental  hemorrhage  over  the  upper 
incisor  teeth,  which  were  erupting,  and  tenderness  of  the 
lower  ends  of  the  femora.  The  scorbutic  nature  of  these 
signs  were  substantiated  by  their  prompt  subsidence  on 
the  administration  of  orange  juice.  We  explain  the  phe- 
nomenon as  follows  :  This  baby  had  been  starved  in  a  two- 
fold sense  throughout  the  first  months  of  its  life — it  had 
received  a  diet  lacking  in  caloric  value  as  well  as  deficient 
in  antiscorbutic  vitamine.  Its  growth  impulse  had  been 
held  in  abeyance  for  months  by  both  of  these  factors. 
When  sufficient  calories  were  supplied  in  the  dietary, 
growth  was  no  longer  repressed,  and  a  steady  gain  re- 
sulted in  spite  of  the  continued  inadequacy  of  the  anti- 
scorbutic factor. 

It  has  been  shown  that  during  the  period  of  infancy 
undernourishment  must  be  extreme  to  occasion  stunting 
of  growth  in  length.  In  animals  Aron  demonstrated  that 
lack  of  nutrition  led  to  a  decrease  of  the  fat  and  of  the 
muscle  of  the  body,  but  that  the  skeleton  nevertheless 
continued  to  grow,  and  the  ash  content  of  the  body  to 
increase.  In  marasmus,  or  infantile  atrophy,  the  baby 
usually  grows  in  length,  although  its  weight  remains  sta- 
tionary or  decreases.  In  scurvy  we  have  shown  that 
there  is  frequently  a  definite  retardation  of  growth  in 
length,  an  observation  which  has  been  recently  confirmed 
by  Epstein  in  babies  which  developed  this  disorder  in  the 
foundling  asylum  of  Prague  during  the  war.  This  fact 
shows  how  profoundly  the  metabolism  must  be  disturbed 
by  this  disorder.  Figure  25  portrays  this  retardation  in 
growth  and  the  sharp  reaction  when  orange  juice  was 
added  to  the  dietary.  It  also  demonstrates  that  the  growth 


216 


SCURVY:    PAST  AND  PRESENT 


impulse  remains  unimpaired  and  capable  of  quick  re- 
sponse when  the  essential  food  factor  is  furnished. 

Fever. — Fever  frequently  accompanies  scurvy.  It  is 
generally  of  a  low  grade,  ranging  between  100°  and 
101,°  as  may  be  seen  in  Fig.  15.  There  is  a  differ- 
ence  of   opinion   as   to   whether  the   rise   of   tempera- 


ftj 

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Fig.  25. — Showing  retardation  of  growth  in  length  during  the  period  when  no  orange  juice 

was  given  and  supergrowth  when  it  was  given  once  more,    O.  J.  =  orange  juice.    O.  P.  J.= 

orange  peel  juice.    Lower  curve  represents  the  normal. 

ture  should  be  considered  as  truly  scorbutic  in  nature, 
as  "scorbutic  fever,"  or  regarded  merely  as  a  condition 
grafted  ujjon  the  nutritional  disturbance.  A  phenome- 
non which  might  seem  to  argue  for  its  essential  scorbutic 
character  is  the  sharp  subsidence  on  giving  antiscorbutic 
food.  On  the  other  hand,  this  may  quite  as  well  be  inter- 
preted   as     due    to    a    secondary    reaction,    checking 


SYMPTOMATOLOGY  AND  DIAGNOSIS  217 

the  absorption  of  toxins  or  bacteria.  High  temperatures — 
for  example,  fever  of  103°  or  over — are  attributable  to  a 
complicating  infection  and  should  lead  to  careful  exam- 
ination for  the  source  of  the  trouble;  pyelitis  should 
particularly  be  borne  in  mind.  In  a  recent  case  fever  of 
uncertain  origin  disappeared  following  the  transfusion 
of  blood. 

We  have  already  considered  numerous  complications 
of  scurvy,  and  shall  therefore  not  go  over  this  ground 
again.  Many  of  them  are  due  to  hemorrhages  or  to 
serous  effusions  in  various  parts  of  the  body.  Another 
large  group  in  adults  as  well  as  in  infants  are  the  result 
of  infection.  The  respiratory  tract  is  particularly  sus- 
ceptible, pneumonia  constituting  the  most  common  cause 
of  death.  In  infants  we  meet  with  frequent  attacks  of 
" grippe,' '  widespread  occurrence  of  nasal  diphtheria, 
i'urunculosis  and  torpid  ulcers  of  the  skin,  pyelitis,  otitis, 
adenitis,  etc.  We  have  encountered  nasal  diphtheria — 
with  typical  bloody  mucous  discharge — so  frequently  in 
connection  with  scurvy,  that  where  this  local  infection 
occurs  among  a  group  of  infants  they  should  be  carefully 
examined  for  latent  or  mild  scurvy.  Aschoff  and  Koch 
recently  have  laid  emphasis  on  the  frequency  with  which 
diphtheria  complicated  scurvy  among  adults  (soldiers). 
Dysentery  is  another  complication  resulting  from  an  in- 
vasion of  bacteria.  Local  infections  occur  more  often  in 
adults  than  in  infants — cervical  adenitis  following  gin- 
gival pyorrhcea,  "bubo"  of  the  groin  following  infection 
of  the  lower  extremity,  abscess  of  the  calf  of  the  leg 
following  hemorrhage  into  this  region. 

Scurvy  sometimes  occurs  in  epidemic  form,  especially 
in  the  army,  but  also,  as  in  Russia,  among  the  civilian 
population.    This  results  when  a  large  group  of  individ- 


218 


SCURVY:    PAST  AND  PRESENT 


uals  have  been  maintained  on  a  limited  and  inadequate 
ration,  and  especially  where  this  nutritional  condition  is 
complicated  by  intercurrent  infection.  It  should  not  be 
interpreted  as  evidence  of  the  bacterial  origin  of  scurvy. 
A  few  years  ago  the  author  reported  an  epidemic  of 
scurvy  in  connection  with  an  outbreak  of  grippe  in  an 
infant  asylum.  Twelve  infants  in  one  ward  were  affected. 
The  signs  were  atypical — an  undue  degree  of  hemorrhage 
occurring  at  atypical  sites  (Table  5).  It  will  be  noted 
from  the  table  that  the  ages  of  the  infants,  the  distribution 


TABLE  5. 
Data  of  Epidemic  of  Scurvy 


Case 


Age. 
Mos 


6V2 


10 


i.  J.  H. 


2.  L.  S. 


3.  A.  R. 


4.   D.  E. 


5-  T.  K.     io 


6.  P.  G. 


7.  I.  P. 


Weight        Site  °f  Hemor- 
rhages 


lbs.  oz. 

9  6 

io  4 

12  14 


12         8 


IS      13 


8        4 


6        4 


Humerus,       tibia, 

face. 
Upper  eyelid 

External  ear,  pari- 
etal bones,  ver- 
tebral column, 
abdominal  wall 


Femur . 


Femur  again  swol- 
len and  tender. 


Both   ears;   parie- 
tal bones. 


Ear  and  face 


Tibia 


Abdomen 


Date 


Diet 


Apr.  19 
May    9 

May   4 


Apr.  19 
June   4 

Apr.  29 

Apr.  27 
May   8 

Mar.  7 


Breast  milk  (i 
week) ;  pasteur- 
ized milk  previ- 
ously. 

Pasteurized  milk 
formula;  orange 
juice  i  oz.  daily 
since  April  22. 


Pasteurized  milk 
formula;  vege- 
tables for  a 
month;  orange 
juice  longer;  get- 
ting orange  juice 
and  vegetables. 

Breast  milk  since 
April  19;  May  30 
changed  to  pas- 
teurized milk. 


Pasteurized  milk, 
cereal,  vegeta- 
ble, soup;  or- 
ange juice  since 
April  15- 

Pasteurized  milk 
formula. 


Breast  milk  for 
past  week;  pas- 
teurized milk 
previously. 


Remarks 


Grippe  since  end  of 
February;  nephri- 
tis; v.  Pirquet  neg- 
ative. 

Twitchings  and  con- 
vulsions; signs  of 
intoxication;  red 
blood  cells  in  urine 
fever  to  101  P.;  v. 
Pirquet  negative. 

Grippe  end  of  Janu- 
ary; again  in  April ; 
fever  until  April 
17;  v.  Pirquet  pos- 
itive ;  gums  nega- 
tive. 

Grippe  throughout 
March;  intoxica- 
tion; nephritis;  no 
relapse  although 
no  orange  juice 
given. 

Two  teeth;  gums 
negative ;  y.  Pir- 
quet negative. 


Grippe  end  of  Feb- 
ruary and  first  half 
of  March  gained 
20  oz.  during  last 
month;  v.  Pirquet 
negative. 

Grippe;  probable 
source  of  epidemic. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  219 

of  the  hemorrhages,  the  development  of  signs  (in  some 
instances)  in  spite  of  antiscorbutic  treatment,  the  sharply- 
defined  epidemic  character,  distinguish  these  cases  from 
the  scurvy  commonly  seen.  This  is  an  instance  where 
latent  scurvy  was  prematurely  changed  to  acute  scurvy 
by  an  intercurrent  ward  infection;  an  epidemic  of  grippe 
precipitated  a  pseudo-epidemic  of  scurvy.  It  is  import- 
ant, especially  for  army  surgeons,  to  bear  in  mind  that 
where  latent  scurvy  exists  a  bacterial  invasion  will  lend 
the  disorder  a  hemorrhagic  character.  This  has  been 
noted  during  the  recent  war  in  connection  with  typhus 
fever  on  the  Eastern  front,  and  was  remarked  upon 
during  the  Crimean  War  and  our  War  of  the  Rebellion. 
Some  years  ago  Wherry  made  a  similar  observation  in 
the  course  of  'experiments  with  the  plague  bacillus — 
guinea-pigs  fed  on  a  cereal  diet  developed  far  more  hemor- 
rhages subsequent  to  infection  than  those  which  received 
cabbage  in  addition. 

DIAGNOSIS 

A  correct  and  early  diagnosis  of  scurvy  is  the  more 
important  in  view  of  the  fact  that  we  possess  a  specific 
remedy,  and  that  the  disorder  is  not  self -limited.  Recog- 
nition generally  presents  little  difficulties  for  those  who 
have  seen  cases,  but  is  a  stumbling  block  where  the  symp- 
tomatology has  been  gleaned  merely  from  the  textbooks. 
It  has  been  our  experience  that  medical  students  who  were 
conversant  with  scurvy  from  a  theoretical  standpoint 
failed  to  diagnose  a  case  presented  to  them  in  the  clinic. 
Where  diagnosis  is  uncertain,  the  most  important  aid 
is  an  exact  knowledge  of  the  previous  diet,  and  observa- 
tion of  the  reaction  of  the  patient  to  antiscorbutic  treat- 
ment.   These  diagnostic  points  should  be  constantly  re- 


220  SCURVY:    PAST  AND  PRESENT 

nienibered  in  relation  to  the  discussion  which  follows, 
and  will  not  be  reiterated  in  the  differentiation  of  scurvy 
from  the  various  other  diseases. 

The  scurvy  of  adults  and  of  infants  are  very  similar. 
The  main  difference  is  the  subjective  symptoms  in  the 
adult — pains  in  various  parts  of  the  body — and  the  fact 
that  the  gums  are  frequently  the  site  of  infection  and 
ulceration,  as  well  as  of  hemorrhage.  It  might  be  thought 
that  when  scurvy  occurs  in  epidemic  form  it  would  be 
readily  recognized,  but  experience  shows  that  for  months 
it  may  permeate  the  ranks  of  troops  or  the  inmates  of 
almshouses,  and  pass  as  rheumatism.  This  is  the  cardinal 
diagnostic  error  in  adult  as  well  as  in  infantile  scurvy — 
time  and  again,  and  in  spite  of  urgent  and  repeated  warn- 
ings, patients  continue  to  be  treated  for  rheumatism. 
Holt  writes :  "In  fully  four-fifths  of  the  cases  which  have 
come  to  my  own  notice  this  (rheumatism)  has  been  the 
previous  diagnosis."  Such  has  been  our  experience. 
The  diagnosis  should  not  be  difficult.  In  sporadic  cases, 
the  individual  has  limited  his  diet  usually  on  account  of 
indigestion,  or  diarrhoea,  or  following  some  dietetic  whim 
or  medical  advice  given  months  previously.  Where 
scurvy  occurs  en  masse  it  may  follow  an  inability  to 
obtain  fresh  food — as  during  war,  on  shipboard,  in  the 
Tropics  or  in  the  Arctic  regions — or  be  the  result  of  a 
misplaced  reliance  on  some  article  of  food — for  example, 
dehydrated  vegetables.  More  careful  investigation  will 
disclose  that  the  "rheumatic"  pains  and  tenderness  are 
not  in  the  joints  but  in  the  muscles  and  tendons.  The 
calf  muscles  are  frequently  painful  and  excessively  ten- 
der and  somewhat  swollen  or  infiltrated;  the  hamstring 
tendons  or  the  tendo-Achilles  may  be  sore  and  slightly 
swollen  and  the  site  of  slight  subcutaneous  hemorrhages. 


SYMPTOMATOLOGY  AND  DIAGNOSIS  221 

In  some  cases  there  is  bone  tenderness,  pain  on  percussion 
of  the  shins  or  of  the  sternum.  These  signs  may  be 
accompanied  by,  or  even  precede,  hemorrhages  in  the 
gums.  The  diagnosis  of  rheumatism  in  infants  indicates 
a  lack  of  knowledge  of  pediatrics,  as  this  disease  is  hardly 
ever  encountered  in  babies  under  a  year  and  a  half  of  age. 

It  is  not  always  easy  to  differentiate  scurvy  from 
purpura.  In  either  disease  the  gums  may  be  hemorrhagic 
and  swollen,  there  may  be  scattered  subcutaneous  hemor- 
rhages and  pains  in  the  limbs.  Occasionally,  as  in  a  case 
seen  a  few  years  ago,  we  may  be  forced  to  resort  to  the 
dietetic  test.  A  close  inquiry  into  the  previous  diet, 
however,  a  history  of  previous  attacks  of  purpura,  the 
number,  and  especially  the  large  size,  of  the  subcutaneous 
hemorrhages,  and  above  all,  the  diminished  number  of 
blood-platelets,  should  make  diagnosis  possible.  In 
scurvy  the  platelets  are  almost  always  over  300,000  per 
cubic  millimetre,  whereas  in  purpura  they  are  reduced 
to  less  than  200,000. 

In  the  army  it  may  be  difficult  to  distinguish  scurvy 
from  beriberi,  especially  if  they  occur  side  by  side  as 
in  the  recent  English  campaign  in  Mesopotamia.  There 
maybe  a  combination  of  the  two  diseases,  a  picture  similar 
to  ship-beriberi,  regarded  by  Nocht  as  a  hybrid  of  these 
diseases.  The  diagnosis  is  rendered  more  difficult,  as 
at  times  scurvy  is  associated  with  signs  of  neuritis.  We 
shall  have  to  depend  on  the  involvement  of  the  gums  and 
the  hemorrhages  in  scurvy,  and  on  the  hyperesthesia, 
paresthesia,  and  anesthesia  in  beriberi;  marked  edema 
points  to  the  latter  disease. 

We  have  thus  far  had  in  mind  frank  and  outspoken 
cases  of  scurvy.  When  we  come  to  consider  latent  or 
early  cases,  the  diagnosis  is  more  difficult  and  may  have 


222  SCURVY:    PAST  AND  PRESENT 

to  be  merely  tentative.  All  that  need  be  added,  in  view 
of  the  clinical  picture  sketched  above,  is  that  this  con- 
dition should  not  be  forgotten  in  treating  adults  who  have 
malaise  and  indefinite  "  rheumatic "  pains  and,  more  par- 
ticularly, in  relation  to  infants  who  fail  to  gain,  whose 
appetite  is  capricious,  whose  disposition  has  become  fret- 
ful and  who  have  developed  the  sallow  scorbutic  complex- 
ion. This  warning  is  particularly  opportune  at  present 
in  the  United  States,  where  pasteurized  milk  is  fed  so 
extensively  to  infants,  and  an  antiscorbutic  food  is  not 
always  given. 

In  addition  to  the  symptoms  just  enumerated,  tender- 
ness of  the  bones,  especially  of  the  distal  ends  of  the 
femora,  should  be  sought  for,  the  urine  should  be  exam- 
ined carefully  for  red  blood-cells,  and  perhaps  the  ends 
of  the  long  bones  radiographed  for  "the  white  line" 
of  Fraenkel. 

The  experience  of  Comby  with  infantile  scurvy  is  illu- 
minating. Among  the  fifty-five  cases  which  he  has  seen, 
the  diagnosis  was  erroneous  in  forty-five,  and  among 
thirteen  cases  recently  met  with,  the  physician  failed  to 
recognize  the  disorder  in  all  but  two.  The  infants  had 
been  given  sodium  salicylate,  had  been  treated  with  elec- 
tricity and  massage  for  the  supposed  acute  poliomyelitis, 
or  given  mercury  for  syphilis,  or  incisions  or  trephining 
had  been  carried  out  for  acute  osteomyelitis.  Some  had 
been  put  into  plaster  casts  for  coxalgia  or  for  Potts ' 
disease.  This  experience  requires  little  comment.  It 
should  be  added,  however,  that  in  the  course  of  an  epi- 
demic of  poliomyelitis,  such  mistakes  are  apt  to  happen, 
and,  to  our  knowledge,  did  occur  in  the  recent  epidemic. 

In  regard  to  "the  pseudo-paralysis"  of  congenital 
syphilis  diagnosed  as  scurvy,  it  should  be  remembered 


SYMPTOMATOLOGY  AND  DIAGNOSIS  223 

that  this  lesion  occurs  almost  always  before  the  fifth  month 
of  life.  A  history  of  previous  papular  eruption,  the 
bilateral  enlargement  of  the  epitrochlear  glands,  and 
the  Wassermann  test  should  suffice  to  establish  the  cor- 
rect diagnosis. 

Besides  the  clinical  conditions  enumerated  above, 
we  may  add  the  following,  which  have  been  confused 
with  scurvy:  Neuritis,  hemorrhagic  nephritis,  cal- 
culus of  the  urinary  tract,  renal  tumor,  orbital  tumor, 
appendicitis,  peritonitis,  pleurisy  and  pneumonia.  Holt 
writes  as  follows:  "I  have  known  two  cases  to  be  oper- 
ated upon  by  eminent  surgeons,  once  with  a  diagnosis  of 
sarcoma  and  once  of  ostitis  of  both  tibiae.  Not  until  the 
subperiosteal  hemorrhages  and  epiphyseal  separations 
were  discovered  was  the  nature  of  the  trouble  suspected. ' ' 
Recently  we  saw  a  case  of  fracture  of  the  distal  end  of  the 
femur  diagnosed  as  infantile  scurvy ;  the  baby  had  caught 
its  thigh  between  the  bars  of  the  crib  and  snapped  the 
bone  in  trying  to  extricate  itself.  Finkelstein  adds  acute 
endocarditis,  hemorrhagic  septicaemia  with  multiple  bone 
swellings,  and  leukaemia  as  having  been  confused 
with  scurvy. 

In  an  interesting  account  of  scurvy  in  the  Russian 
army  during  the  recent  war,  Hoerschelmann  states  that 
tired  soldiers  at  times  feign  scurvy.  They  produce  a 
"pseudo-scurvy"  by  means  of  scratching  the  gums  with 
their  nails  or  rubbing  them  with  tobacco,  and  at  the  same 
time  bring  about  hemorrhages  of  the  skin  by  means 
of  trauma. 

Scurvy  in  the  breast-fed  infant  has  been  fully  con- 
sidered under  etiology.  We  wish  merely  to  state  again 
that  one  cannot  be  too  cautious  in  venturing  this  diag- 
nosis in  a  nursing  baby.    The  great  majority  of  reported 


224  SCURVY:    PAST  AND  PRESENT 

cases  are  not  scurvy,  but  bacterial  infections,  syphilis,  or 
various  forms  of  intoxication.  In  establishing  a  diag- 
nosis the  same  principles  hold  as  in  the  case  of  bottle- 
fed  infants. 

The  most  important  consideration  in  the  diagnosis  of 
scurvy  is  to  keep  in  mind  the  heterogeneous  character  of 
its  symptoms,  and  the  manifold  diseases  with  which  it 
may  be  confused.  Surgeons  should  be  alert  to  this  danger 
when  about  to  perform  operations  for  osteomyelitis  or 
bone  tumor.  The  mistakes  occur  because  cases  are  infre- 
quently seen  and  because  the  signs,  being  dependent 
largely  upon  hemorrhage,  occur  in  such  varied  locations 
of  the  body.  Where  diagnosis  cannot  be  made  from  the 
signs  or  symptoms,  the  most  important  aid  is  a  thorough 
acquaintance  with  the  previous  diet  of  the  individual  and 
observation  of  his  reaction  to  antiscorbutic  treatment. 


CHAPTER   VIII 
PROGNOSIS 

The  outcome  of  scurvy,  as  we  encounter  it  in  peace 
time  in  the  Temperate  Zone,  is  generally  favorable,  so  that 
it  plays  but  an  insignificant  role  in  our  mortality  statis- 
tics. This  results  from  the  fact  that  we  are  abundantly 
provided  with  a  specific  remedy,  so  that  if  the  diagnosis 
is  made  early  and  treatment  is  prompt  and  thorough, 
the  patient  will  rapidly  recover  and  suffer  no  physical 
disability.  Where  antiscorbutic  foodstuffs  are  not  pro- 
curable, however,  this  disease  constitutes  a  terrible 
scourge,  causing  many  deaths  and  spreading  among  an 
army,  a  ship's  crew,  or  among  the  civil  population  with 
the  rapidity  of  an  epidemic.  For  example,  the  ships  of 
the  East  India  Company  in  their  voyages  round  the  Cape 
often  lost  nearly  one-half  of  their  crews,  and  in  Lord 
Anson's  famous  voyage  round  the  world  380  out  of  510 
seamen  perished  from  the  disease.  Moreover,  if  the  anti- 
scorbutic treatment  is  inadequate  or  the  patient  goes 
untreated  for  a  long  period,  the  cure  may  be  incomplete, 
a  condition  of  malnutrition  and  weakness  developing, 
which  may  persist  for  years.  To  appreciate  this  clinical 
condition  we  must  refer  to  the  account  of  physicians  who 
saw  thousands  of  cases  of  severe  and  untreated  scurvy 
among  the  sailors,  who  were  of  necessity  deprived  of  aid 
until  they  reached  land.  Lind  laid  stress  on  a  type  of 
this  disease  which  developed  under  these  circumstances 
and  which  he  termed  "obstinate  scurvy."  He  writes: 
"I  have  met  with  numerous  instances  not  only  among 
the  common  seamen,  but  of  officers,  with  whom  it  had 

15  225 


226  SCURVY:    PAST  AND  PRESENT 

taken  such  deep  root  in  the  constitution  as  to  prove  a 
lasting  affliction  to  them  during  a  great  part  of  their  lives. 
.  .  .  Persons  are  likewise  subject  in  different  periods 
of  their  life  afterwards  to  habitual  rheumatism,  pains  and 
stiffness  in  their  joints;  and  sometimes  eruptions  on  the 
skin."  In  his  treatise  on  scurvy,  published  in  1685, 
Harvey  refers  to  this  chronic  nutritional  disorder  as 
'  ■  inveterate  scurvy. ' '  He  pictures  patients  who  had  gone 
untreated  for  a  long  time  as  "molested  with  vagrant, 
ambulative,  distending,  creeping,  vellicating  or  lancinat- 
ing pains  of  several  parts  of  the  body.  .  .  .  They  are 
often  loose  and  subject  to  falling  into  violent  fluxes  of  the 
belly,  diarrhoea  and  lienteries." 

Infants  as  well  as  adults  usually  recover  rapidly  and 
completely  from  scurvy,  the  result  depending  largely  upon 
the  early  recognition  of  the  disease.  We  must  always 
bear  in  mind,  however,  that  from  a  histologic  standpoint 
the  cure  is  not  simultaneous  with  the  magic  disappear- 
ance of  the  clinical  symptoms,  but  that  months  probably 
elapse  before  the  tissues  return  to  their  normal  state. 
It  is  difficult  to  give  reliable  mortality  statistics  for  infan- 
tile scurvy,  for  so  many  cases  are  of  the  rudimentary 
form  that  percentages  are  necessarily  misleading.  Still 
writes  that  in  5  out  of  64  cases  the  disease  proved  fatal 
by  diarrhoea  and  exhaustion.  The  American  Pediatric 
Society  reports  29  deaths  out  of  397  cases,  which  gives  a 
similar  mortality  percentage.  When  infantile  scurvy  was 
not  so  generally  recognized  by  physicians  the  mortality 
was  much  higher,  and  we  find  that  Barlow  encountered 
7  deaths  in  his  first  series  of  31  cases. 

Even  when  the  child  recovers  it  may  not  regain  its 
normal  health  if  it  has  continued  for  a  prolonged  period  in 
a  state  of  chronic  scurvy.    It  may  remain  pale  and  fail  to 


PROGNOSIS  227 

gain  in  weight  in  spite  of  a  liberal  and  well-balanced  diet. 
Cases  of  this  kind  are  not  infrequent.  In  this  connection 
it  is  worthy  of  note  that  4  of  the  41  cases  of  "cceliac  dis- 
ease," an  interesting  intestinal  condition  described  by 
Still,  had  scurvy  just  before  or  during  the  onset  of  the 
disease.  This  observation  conforms  to  the  experience 
that  chronic  bowel  disorders  often  follow  in  the  wake  of 
adult  scurvy. 

In  adults  the  heart  may  be  weakened  by  scurvy,  and 
death  may  result  from  cardiac  failure.  Cardiac  disturb- 
ances occur  also  in  infantile  scurvy.  This  involvement 
might  be  expected,  in  view  of  the  tachycardia  (cardio- 
respiratory phenomenon)  which  is  so  frequent  a  symptom 
of  infantile  scurvy.  The  heart  may  be  rapid  for  months 
or  even  for  years  after  the  disorder,  and  tachycardia 
may  develop  on  the  occasion  of  even  a  mild  infectious  dis- 
ease. For  example,  a  fever  of  101°,  due  to  a  common 
coryza,  may  cause  the  heart-beat  to  rise  to  perhaps  180 
a  minute.  Children  so  affected  succumb  readily  to  infec- 
tion, especially  to  pneumonia,  which  may  lead  to  sudden 
collapse  followed  by  death. 

An  important  factor  in  the  prognosis  of  scurvy,  as  in 
that  of  other  disorders  due  to  a  lack  of  vitamines,  is  the 
marked  susceptibility  to  infection.  Even  latent  or  sub- 
acute scurvy  causes  a  peculiar  susceptibility  to  diph- 
theria (especially  the  nasal  type),  to  coryza,  bronchitis, 
and  pneumonia.  A  perusal  of  the  literature  shows  that 
this  susceptibility  was  noted  by  the  older  authors  in 
relation  to  adults. 

The  local  signs  usually  disappear  quickly  without  leav- 
ing any  trace.  The  hemorrhages  are  absorbed  and  the 
eczema  heals  within  a  few  days.  The  fractures  unite 
promptly  with  the  formation  of  an  unusually  large  callus. 


228  SCURVY:    PAST  AND  PRESENT 

The  urine,  which  may  have  contained  red  blood-cells  or 
have  been  markedly  hemorrhagic,  quickly  becomes  normal 
and,  in  our  experience,  gives  no  further  evidence  of  renal 
damage.  Still  reports,  however,  the  case  of  a  frail  child 
who  had  a  trace  of  albumen  in  the  urine  two  years  after 
an  attack  of  scurvy.  A  rare  local  injury,  which  may  lead 
to  death,  is  cerebral  hemorrhage.  Recently  Sammis  re- 
ported a  case  of  this  kind,  which  was  characterized  by 
convulsions  during  life,  and  in  which  subdural  hemor- 
rhage was  found  at  necropsy. 

If  we  acknowledge  an  individual  idiosyncrasy  to 
scurvy  we  should  expect  a  tendency  to  a  recurrence  of 
the  disease.  Lind  was  of  this  opinion,  stating  that  "by 
observations  made  on  this  disease,  it  appears  that  those 
who  are  once  afflicted  with  it,  especially  in  so  high  a  de- 
gree as  that  squadron  was,  are  more  subject  to  it  after- 
wards than  others.' '  It  is  difficult  at  the  present  day  to 
express  a  personal  opinion  on  this  matter,  as  clinical 
experience  is  meagre  and  the  scurvy  of  guinea-pigs  is  so 
acute  that  it  cannot  be  used  for  comparison.  Some  of  the 
recurrences  have  been  due  probably  to  the  fact  that  the 
patient  had  not  been  completely  cured  of  his  first  attack. 
"VVe  have  met  with  two  cases  of  recurrences  in  infants,  one 
of  which  is  of  particular  interest  as  it  happened  in  spite 
of  giving  lemon  juice  in  the  intervening  period.  The  his- 
tory was  as  follows : 

In  September,  1914,  one  month  after  the  baby  was 
admitted  to  the  institution,  it  developed  scurvy  of  a  mod- 
erate grade.  It  was  then  six  months  of  age  and  weighed 
10-/4  pounds.  It  was  put  on  a  simple  mixture  containing 
from  24  to  30  ounces  of  pasteurized  milk  and  was  given 
in  addition  %  ounce  of  lemon  juice  a  day.  It  improved, 
but  during  the  winter  had  bronchitis,  otitis,  enteritis,  and 


PROGNOSIS  229 

later  furunculosis.  In  spite  of  the  fact  that  it  had  been 
receiving  an  antiscorbutic  for  almost  this  entire  period, 
it  developed  scurvy  once  more  in  February,  at  the  age 
of  11  months,  and  when  it  weighed  M1/^  pounds.  It  was 
evident  that  this  baby  was  peculiarly  susceptible  to 
scurvy.  It  may  be  added  that  the  second  attack  was 
complicated  by  nasal  diphtheria. 

In  this  connection  attention  should  be  drawn  to  a 
peculiar  and  puzzling  clinical  phenomenon,  which  we  have 
noted  several  times.  Even  if  the  antiscorbutic  treatment 
is  carried  out  incompletely  and  only  for  a  short  period, 
recrudescences  may  not  take  place.  We  have  seen  cases 
where  orange  juice  was  given  for  merely  ten  days  or  two 
weeks — that  is,  only  until  all  scorbutic  signs  had  disap- 
peared,— and  yet  the  scurvy  did  not  return,  the  infants 
thrived  for  months  thereafter,  but  were  merely  somewhat 
pale  and  undernourished.  In  the  case*  of  two  babies 
which  we  have  in  mind,  the  diet  remained  absolutely  un- 
changed, with  the  exception  of  the  short  period  of  anti- 
scorbutic treatment,  but  this  seemed  sufficient  to  bring 
about  a  diminished  susceptibility. 


CHAPTER  IX 
TREATMENT 

"Seek  the  cure  of  scurvy  neither  in  the  armamen- 
tarium of  the  physician  nor  in  the  apothecary  shops.  The 
druggist  will  be  of  as  little  aid  to  you  as  the  art  of  the 
surgeon.  On  the  other  hand,  employ  fresh  vegetables, 
the  juice  of  fresh  antiscorbutic  plants,  oranges  and  lemons 
or  the  juice  of  those  fruits  preserved  with  sugar;  in 
this  way  without  other  means  you  will  be  able  to  over- 
come this  terrible  disease.' '  This  reads  like  the  advice 
of  some  modem  therapeutist;  it  is,  however,  the  conclu- 
sion of  a  physician  (Kramer)  who  wrote  on  scurvy  almost 
two  hundred  years  ago,  and  shows  that  the  treatment  of 
scurvy  has  undergone  no  fundamental  change  in  the  inter- 
vening years.  Our  resources,  however,  have  been  ampli- 
fied by  an  increased  knowledge  of  the  relative  value  of 
antiscorbutic  foodstuffs  and  by  the  introduction  of  some 
new  ones. 

Prevention. — In  the  Temperate  Zone,  under  ordinary 
conditions,  the  adult  population  consumes  sufficient  anti- 
scorbutic foodstuff  to  protect  it  from  scurvy.  Under  ex- 
ceptional circumstances,  however — for  example,  when  the 
potato  crop  fails,  or,  in  the  case  of  individuals,  when  the 
diet  has  been  unduly  restricted,  scurvy  will  be  encoun- 
tered. This  disorder  is  still  an  important  problem,  how- 
ever, in  relation  to  the  health  of  adults  in  the  Tropics, 
in  military  expeditions  and  in  Polar  explorations.  From 
what  has  been  stated  in  the  preceding  chapter,  it  is  evi- 
dent that,  at  the  present  time,  no  reliance  can  be  placed 
on  dehydrated  vegetables  as  a  protective  agent.     The 

230 


TREATMENT  231 

recent  suggestion  of  using  germinated  dried  pulses  and 
seeds,  under  circumstances  where  fresh  food  is  not  avail- 
able, is  practical  and  probably  will  be  resorted  to  in  the 
future.  To  this  end  the  pulses  (beans,  peas,  lentils)  are 
soaked  in  water  for  24  hours,  and  then  kept  moist  with 
access  of  air  for  about  48  hours  at  room  temperature. 
During  this  period  they  sprout  and  develop  small  radicles. 
They  are  cooked  in  the  usual  way  and  have  been  found  to 
possess  an  antiscorbutic  value  comparable  to  that  of  most 
vegetables.  An  individual  should  receive  about  four 
ounces  a  day  of  these  sprouted  seeds.  In  the  treatment  of 
some  Serbian  soldiers  suffering  from  scurvy,  Wiltshire 
found  that  this  amount  of  germinated  beans  brought  about 
a  cure.  There  are,  however,  two  drawbacks  to  their  gen- 
eral use.  The  prolonged  cooking  necessary  for  their 
preparation  reduces  their  antiscorbutic  potency,  and  they 
have  been  found  indigestible  when  consumed  in  suffi- 
cient quantity. 

Under  similar  conditions  canned  tomatoes  can  be  em- 
ployed; they  have  the  disadvantage  of  greater  bulk,  but 
are  a  more  potent  antiscorbutic,  require  no  preparation 
whatsoever,  and  are  readily  digested.  They  form  part  of 
the  present  ration  of  the  United  States  Army,  in  which 
they  can  be  given  "in  lieu  of  an  equal  quantity  of  pota- 
toes not  exceeding  twenty  per  cent,  of  the  total  issue."  * 
The  necessity  of  including  an  antiscorbutic  in  the  army 
ration  has  been  recognized  only  in  recent  years;  during 
our  Civil  War  and  for  thirty  years  thereafter  there  was 

1  We  have  been  unable  to  ascertain  through  inquiries  from  the  Sur- 
geon-General's Office  the  nature  of  the  experience  which  led  to  their  incor- 
poration in  the  ration,  and  whether  they  were  added  specifically  as  an  anti- 
scorbutic. They  appear  for  the  first  time  in  the  revision  of  the  Army  Regu- 
lations of  1895.  The  only  reference  to  the  antiscorbutic  property  of  canned 
tomatoes  which  we  have  been  able  to  find  in  the  literature  is  in  the  excellent- 
treatise  by  Munson  on  Military  Hygiene, 


232  SCURVY:    PAST  AND  PRESENT 

no  such  provision.  It  was  stated  at  that  time  that  a 
general  scorbutic  taint  pervaded  the  troops — a  mere 
euphemism  for  the  widespread  existence  of  subacute  or 
latent  scurvy.  Even  to-day  the  ration  of  the  French  and 
of  the  Italian  armies  makes  no  definite  provision  in  this 
regard  and  the  Russians  provide  merely  for  a  variable 
quantity  of  vegetables. 

Recently  it  has  been  shown  that  lemon  and  orange 
juices  (Givens  and  McClugage)  can  be  dried  and  still 
preserve  their  antiscorbutic  value.  It  is  quite  possible 
that  concentrated  preparations  of  this  kind  will  be  ser- 
viceable for  army  use  and  in  regions  where  fresh  fruit  or 
vegetables  cannot  be  obtained.2 

Lind  makes  numerous  ingenious  suggestions  for  pre- 
paring antiscorbutic  remedies  (Lind,  pp.  7,  8  and  9)  which 
have  a  practical  as  well  as  historic  interest.  (Appen- 
dix 1.)  One  of  these  includes  a  formula  for  the  prepara- 
tion of  orange  and  lemon  juice  which  may  be  preserved 
for  years ;  another  gives  a  method  for  the  preservation  of 
berries  and  other  fruits  which  are  to  be  picked  when 
partly  ripe  and  put  up  in  earthen  pots ;  still  another  gives 
the  recipe  for  preparing  a  simple  decoction  of  fir  tops, 
which  was  found  by  the  Swedes  efficacious  in  preventing 
the  development  of  scurvy  among  their  soldiers.  It  is 
interesting  that  a  similar  practice  was  resorted  to  in 
Vienna  during  the  recent  war  and  recommended  as  a 
prophylactic  for  scurvy  in  children  (Tobler). 

3  Since  the  above  was  written,  an  article  has  appeared  by  P.  W.  Bas- 
sett-Smith  (Scurvy:  With  Special  Reference  to  Prophylaxis  in  the  Royal 
Navy.  Lancet,  London,  1920,  I,  1102)  showing  that  lemon  juice  can  be  pre- 
pared in  tablet  form  and  preserve  its  efficacy  for  at  least  three  months. 
Each  tablet  contained  the  equivalent  of  24  c.c.  of  lemon  juice,  and  less  than 
one-fifth  of  a  tablet  was  sufficient  to  protect  a  guinea-pig  from  scurvy.  This 
therapeutic  procedure  seemH  of  great  promise  in  providing*  an  antiscor- 
butic ration  for  the  navy  or  the  army. 


TREATMENT  233 

The  prevention  of  infantile  scurvy,  especially  in  its 
rudimentary  form,  is  of  great  practical  importance,  be- 
cause of  its  frequent  occurrence.  There  is  no  question 
but  that  breast  milk  and  raw  cow's  milk  furnish  sufficient 
antiscorbutic  vitamine,  but  there  is  a  difference  of  opinion 
as  to  whether  pasteurized  milk,  or  milk  that  has  been 
brought  just  to  the  boiling-point,  or  even  sterilized  milk, 
is  adequate  in  this  respect.  Much  of  this  divergence  of 
opinion  is  due  to  the  fact  that  the  various  clinicians  have 
not  considered  or  stated  the  quantity  of  milk  which  they 
have  found  sufficient  to  protect,  and  also  because  milk 
itself  differs  in  its  antiscorbutic  value  according  to  its 
freshness  and  probably  also  according  to  the  fodder  of 
the  cows.3  Without  entering  once  more  into  a  discussion 
of  this  question,  it  may  be  stated  that  unless  the  cow's 
milk  is  raw,  the  infant  should  receive  additional  antiscor- 
butic foodstuff.  Moreover,  this  supplement  to  the  die- 
tary should  be  made  as  soon  as  possible,  so  as  not  to 
allow  the  vitamine  deficiency  and  inadequate  diet  to  exist 
for  even  a  short  period.  In  our  experience  there  is  no 
contra-indication  to  the  giving  of  orange  juice  or  of 
strained  canned  tomato,  the  two  antiscorbutics  with  which 
we  have  had  a  large  experience,  to  babies  one  month  of 
age  or  even  younger.  The  common  practice,  however, 
is  to  wait  until  the  infant  is  Hive  or  six  months  of  age,  which 

3  It  is  not  possible  to  say  exactly  how  much  raw  milk  a  baby  needs  to 
protect  it  against  the  development  of  scurvy.  We  may,  however,  reach  an 
approximate  estimation  of  this  figure.  We  know  that  it  takes  about  2  c.c. 
of  orange  juice  to  protect  a  guinea-pig  against  manifest  scurvy,  and  about 
10  c.c.  to  protect  a  baby.  The  ratio,  therefore,  between  the  guinea-pig  and 
the  infant  in  this  regard  would  seem  to  be  about  5  to  1.  We  also  know  that 
it  takes  about  80  to  100  c.c.  daily  of  fresh  cow's  milk  to  protect  a  guinea- 
pig  for  long  periods.  If  we  assume  the  ratio  of  5  to  1,  it  would  therefore 
seem  that  it  would  require  about  500  c.c.  or  a  pint,  of  fresh  raw  milk 
daily  as  a  minimum  to  protect  the  baby.  (It  is  quite  possible  that  a  slight 
negative  balance  of  the  vitamine  may  exist  unless  a  still  greater  amount 
is  given.) 


234  SCURVY:    PAST  AND  PRESENT 

certainly  must  allow  a  rudimentary  scorbutic  condition  to 
develop.  At  the  age  of  a  month  one  teaspoonful  of  orange 
juice  may  be  given;  it  should  be  diluted  with  water  and 
sugar  added  if  it  is  tart.  This  may  be  administered  not- 
withstanding the  fact  that  a  baby  has  a  tendency  to  loose- 
ness of  the  bowels,  as  orange  juice,  as  recently  pointed 
out  by  Gerstenberger,  has  practically  no  laxative  action. 
Occasionally  babies  regurgitate  orange  juice,  but  the  reac- 
tion usually  ceases  after  a  day  or  two.  If  it  does  not,  a 
small  amount  of  an  alkali — for  example,  limewater  or 
sodium  bicarbonate — may  be  added  just  previous  to  feed- 
ing ;  in  this  state  the  juice  will  be  better  tolerated.4  The 
amount  of  orange  juice  should  be  increased  so  that 
when  the  baby  is  three  months  of  age  it  receives 
one  tablespoonful. 

A  few  years  ago  Hess  and  Fish  recommended  the  use 
of  an  infusion  of  orange  peel  in  infant  feeding.  The  peel 
was  finely  grated,  soaked  overnight  in  water  (1  ounce 
of  the  peel  to  2  ounces  of  water),  and  a  small  amount  of 
sugar  added  to  this  liquid.  Animal  experiments  showed 
that  this  preparation  possessed  decided  antiscorbutic 
value.  This  decoction  may  well  be  used  for  the  sake  of 
economy,  and  even  when  the  orange  juice  is  employed  the 
infusion  of  the  peel  may  be  added. 

An  antiscorbutic  which  vies  with  orange  or  with  lemon 
juice  in  adaptability  for  infant  feeding  is  canned  tomatoes, 
as  recently  suggested  by  Hess  and  Unger.  Tomatoes  are 
not  in  good  repute  among  food  experts  in  view  of  the 
small  amount  of  calories  which  they  contain — only  about 

*  Orange  juice  undergoes  a  decided  color  change  as  soon  as  it  has 
become  neutral  or  very  slightly  alkaline,  assuming  a  more  translucent 
and  far  deeper  yellow  or  amber  color.  This  change  may  be  utilized  by  the 
attendant  in  determining  the  reaction,  thus  rendering  titration  or  other 
time-consuming  methods  unnecessary. 


TREATMENT  235 

100  to  the  pound — and  are  regarded  with  suspicion 
amounting  almost  to  superstition  by  mothers  and  nurses 
as  a  food  for  children.  In  spite  of  this  fact,  it  may  be 
stated  without  hesitation  that  they  are  fully  as  well  borne 
by  infants  a  few  weeks  or  months  of  age  as  orange  or 
lemon  juice.  In  considering  antiscorbutics,  it  has  been 
shown  that  notwithstanding  the  canning  process  and 
subsequent  aging,  they  preserve  their  potency.  The  dose 
is  two  tablespoonfuls  for  babies  over  three  months  of  age. 
The  tomatoes  are  merely  strained  through  a  colander  and 
warmed  (not  cooked).  To  illustrate  their  innocuous  char- 
acter, it  may  be  added  that  as  much  as  6  and  8  ounces 
a  day  of  this  juice  have  been  given  to  a  baby  under  one 
year  of  age  without  producing  untoward  symptoms.  This 
antiscorbutic  should  have  wide  applicability,  especially 
in  the  United  States.5 

Another  antiscorbutic  which  can  be  used  in  a  routine 
way  to  prevent  infantile  scurvy  is  swede  juice,  prepared 
by  grating  the  raw  vegetable  and  squeezing  the  pulp  in 
muslin.  Chick  and  Rhodes  report  that  this  juice  has 
been  adopted  for  use  in  some  of  the  English  infant- 
welfare  centres.  It  should  be  given  in  about  the  same 
dosage  as  the  tomatoes,  and  seems  applicable  where  the 
swede  can  be  readily  obtained. 

For  babies  over  six  months  of  age,  reliance  may  be 
placed  on  the  ordinary  household  vegetables — potatoes, 
spinach,  carrots,  squash,  etc.  Attention  should  be  paid 
to  the  amount  which  is  taken,  as  one  or  two  teaspoonfuls 
of  a  vegetable  which  is  poor  in  antiscorbutic  power,  such 

6  There  is  no  relation  whatever  between  the  acidity  of  canned  vege- 
tables and  their  possible  contamination  with  tin.  Experiments  carried  out 
to  determine  this  question  demonstrated,  for  example,  that  a  "  sample  of 
red  kidney  beans  snowing  the  highest  acidity  contained  the  least  tin,"  and 
that  those  samples  containing  the  most  tin  were  all  relatively  low  in 
acidity.     (Report  of  Conn.  Agric.  Station  Bull.  200,  1917,  J.  P.  Street.) 


236  SCURVY:    PAST  AND  PRESENT 

as  carrots  or  beets,  will  be  insufficient  to  protect  against 
scurvy.  Especially  is  this  true  if  the  vegetables  are  old 
and  stale  and  are  cooked  for  a  long  period;6  some  years 
ago  two  infants  under  our  care  developed  scurvy  in  spite 
of  a  small  daily  ration  of  vegetables. 

Potato  in  the  amounts  usually  consumed  is  a  valuable 
antiscorbutic.  It  is  not  an  exaggeration  to  state  that  it 
is  the  main  antiscorbutic  bulwark  of  man.  In  giving 
baked  potato  to  children  it  is  commonly  advised  to  use 
the  floury  part  just  beneath  the  peel;  this  should  be  put 
through  a  sieve  and  mixed  thoroughly  with  boiled  milk 
so  as  to  constitute  a  cream ;  for  younger  babies  it  can  be 
prepared  with  water  to  form  a  diluent  similar  to  the 
barley  water  so  commonly  employed  to  dilute  cow's  milk 
(1  tablespoonful  of  potato  to  a  pint  of  milk,  cooked  for 
15  minutes).  Little  reliance  should  be  placed  on  beef 
juice  in  the  usual  dosage  and  none  on  eggs. 

Cure. — There  is  almost  nothing  in  the  realm  of  therapy 
which  is  so  striking  as  a  scorbutic  patient's  prompt  reac- 
tion to  antiscorbutic  treatment.  It  is  all  the  more  mar- 
velous as  the  cure  is  effected  by  means  of  foodstuffs  with 
which  we  are  accustomed  to  associate  no  specific  virtue. 
A  magic  result  is  seen  frequently  within  24  or  48  hours. 
A  baby  which  has  had  a  poor  appetite,  has  been  irritable 
and  exquisitely  tender,  suddenly  regains  its  appetite,  is  no 
longer  fretful,  and  can  be  handled  without  occasioning 
crying.  Within  a  week,  if  the  case  is  mild,  all  definite 
symptoms  of  scurvy  may  have  disappeared,  and  soon 
thereafter  the  infant  is  thriving  and  apparently  cured. 
A  table  is  here  reproduced  (Table  6)  from  the  report  of 

•Salant,  in  experiments  on  rabbits,  found  that  old  or  winter  carrots 
did  not  have  the  same  protective  action  against  tartrates  as  young  carrots, 
although  their  diuretic  action   is  the  same. 


TREATMENT 


237 


the  American  Pediatric  Society  showing  the  duration  of 
treatment  before  marked  improvement  was  noticed : 

TABLE  6. 
Duration  of  Treatment  Before  Marked  Improvement  was  Noticed 


Days 

Cases 

Weeks 

Cases 

Months 

Cases 

I 

19 

I 

47 

I 

6 

2 

58 

2 

27 

2 

4 

3 

46 

3 

8 

3 

4 

4 

26 

4 

1 

5 

19 

5 

1 

6 

1 

6 

1 

7 

2 

8 

2 

9 

1 

10 

7 

12 

2 

In  most  instances  a  gain  of  weight  accompanies  improve- 
ment. In  not  a  few  instances,  however,  there  is  a  tem- 
porary loss  or  cessation  of  weight,  due  in  part  to  an 
increased  excretion  of  urine.  Occasionally  there  is  ob- 
served a  short  exacerbation  of  the  symptoms  following 
the  giving  of  an  antiscorbutic — a  swelling  of  the  thigh 
or  hemorrhage  of  the  gums.  A  similar  phenomenon  has 
been  noted  in  relation  to  the  treatment  of  polyneuritis 
in  birds  and  of  beriberi  in  man. 

In  the  cure  of  scurvy  the  same  dietetic  remedies  are 
employed  as  in  its  prevention.  Orange  juice  is  the  sover- 
eign remedy,  and  should  be  given  in  a  dosage  of  about 
2  ounces  a  day.7  Canned  tomato  is  also  most  efficacious. 
If  these  changes  in  the  dietary  are  carried  out,  it  is  not 
absolutely  necessary  to  alter  the  food,  although  it  is 
advisable  to  do  so.    Some  writers,  for  example  Neumann 

7  It  is  difficult  to  state  the  exact  dosage  of  orange  juice  which  is  neces- 
sary. One  teaspoonful  daily  has  failed  to  cure,  and  rapid  cures  have  been 
accomplished  by  giving  one  tablespoonful.  It  is  well,  however,  to  give  a 
larger  amount  if  it  is  tolerated. 


238  SCURVY:    PAST  AND  PRESENT 

and  Czerny,  treat  the  disorder  by  giving  milk  which  has 
been  scalded  or  brought  to  the  boiling-point.  Others  lay 
particular  stress  on  changing  the  source  of  the  milk  sup- 
ply, believing  that  the  sameness  of  the  diet  leads  to  the 
occurrence  of  scurvy.  Such,  however,  cannot  be  the  case, 
as  otherwise  breast-fed  babies  would  be  highly  subject 
to  this  disease.  In  the  report  of  the  American  Pediatric 
Society  one  case  developed  on  condensed  milk  and  was 
cured  by  sterilized  milk,  and  another  developed  on  pas- 
teurized milk  and  was  cured  by  sterilized  milk  and  broths. 
These  results  are  explicable ;  large  amounts  of  milk  were 
given  to  effect  the  cure.  It  may  be  said  in  general  that 
in  addition  to  giving  fruit  or  vegetable  juices  the  milk 
should  be  either  raw  or  heated  to  as  low  a  degree  as  pos- 
sible (duration  of  heating  as  well  as  height  of  tempera- 
ture). Furthermore,  the  antiscorbutic  treatment  should 
be  continued  for  a  period  of  months,  as  the  clinical  im- 
provement far  outstrips  the  restoration  of  the  bones  and 
other  tissues.  It  seems  necessary  again  to  call  attention 
to  the  fact  that  too  great  reliance  has  been  placed  on  the 
use  of  beef  juice,  which  has  been  shown,  both  in  experi- 
ment and  in  the  clinic,  to  possess  comparatively  weak 
antiscorbutic  properties. 

Orange  juice  may  be  given  intravenously.  This  method 
may  be  resorted  to  where  the  patient  is  in  an  advanced 
stage  of  the  disease  or  where  food  cannot  be  tolerated  by 
mouth;  for  example,  in  cases  such  as  that  mentioned  by 
Cheadle,  where  death  took  place  owing  to  the  fact  that 
the  antiscorbutic  could  be  taken  only  sparingly,  on  account 
of  the  extreme  prostration  of  the  patient.  For  this 
purpose  the  orange  juice  is  obtained  in  as  sterile  a  manner 
as  possible,  boiled  for  about  five  minutes  and  is  rendered 
neutral  or  slightly  alkaline  just  previous  to  its  injection 


TREATMENT  239 

by  the  addition  of  normal  sodium  hydroxide.  Hess  and 
Unger  report  three  cases  where  this  procedure  was  car- 
ried out  without  the  slightest  untoward  reaction.  In  one 
instance,  improvement  was  noted  16  hours  after  the  in- 
jection. In  view  of  the  novelty  of  this  treatment  it  may 
be  of  interest  to  cite  a  case : 

A  baby  16  months  old  had  hemorrhage  of  the  gums 
and  tenderness  of  the  legs,  which  were  held  in  the  charac- 
teristic flexed  and  everted  position.  Eliminative  treat- 
ment was  tried  without  avail;  Dover's  powder  and 
warmth  to  promote  perspiration;  caffeine  to  promote 
diuresis ;  and  2  tablespoonfuls  of  liquid  petrolatum  three 
times  a  day  to  increase  elimination  from  the  bowels.  In- 
travenous injections  of  salt  solution  also  proved  of 
no  value. 

Four  intravenous  injections  of  orange  juice  were  given 
— 6  c.c.,  12  c.c.,  6  c.c.,  and  35  c.c.  As  was  stated,  improve- 
ment was  noted  16  hours  after  the  first  injection.  The 
infant  was  less  irritable,  the  gums  no  longer  hemorrhagic, 
and  the  "capillary  resistance  test"  (that  is  to  say,  the  de- 
velopment of  petechial  spots  on  the  forearm  when  a 
tourniquet  was  applied  for  3  minutes  to  the  upper  arm) 
changed  from  positive  to  negative. 

Harden,  Zilva  and  Still  have  recommended  the  use  of  a 
concentrated  lemon  juice  for  the  cure  of  scurvy,  constitut- 
ing a  form  of  1 1  intensive ' '  treatment.  In  four  cases  this 
proved  to  be  of  clinical  value.  Freise  has  made  use  of  an 
alcoholic  extract  of  turnips,  and  Freudenberg  of  a  similar 
extract  of  carrots.  These  preparations  did  not  seem  to 
be  markedly  potent,  and  therefore  possess  no  particular 
therapeutic  advantages. 

Non-dietetic  Therapy. — There  is  little  to  be  done  for 
the  patient  in  addition  to  the  giving  of  sufficient  antiscor- 


240  SCURVY:    PAST  AND  PRESENT 

butic.  No  one  has  reported  success  with  any  drug.  We 
have  tried  the  use  of  atropin,  adrenalin,  thyroid  and 
parathyroid  extracts,  cod  liver  oil,  autolyzed  yeast,  lac- 
tose, sodium  chloride,  calcium  chloride,  etc.,  without  not- 
ing any  improvement.  Mercurials  are  stated  to  be 
positively  harmful,  especially  when  ulcers  are  present. 
The  patient  should  be  kept  in  bed,  and  exertion  not 
allowed  on  account  of  the  involvement  of  the  heart,  which 
has  led  to  sudden  collapse  and  death.  The  gums  may  be 
treated  with  nitrate  of  silver  stick  or  tincture  of  myrrh. 
If  there  is  fracture  of  the  long  bones  with  displacement, 
splints  should  be  applied.  Under  no  circumstances  should 
hemorrhagic  effusions  in  or  about  the  joints  be  incised. 
The  patient  should  be  placed  in  a  room  which  is  well 
aired  and  lighted,  and  should  be  handled  and  dressed  as 
infrequently  as  possible,  so  as  to  avoid  discomfort  and 
pain.  It  is  particularly  important  that  intercurrent  in- 
fections should  be  avoided  by  shielding  patients  from 
contact  with  those  who  have  infectious  diseases,  especially 
respiratory  infections. 


CHAPTER  X 
METABOLISM 

Studies  of  the  chemical  exchanges  in  scurvy  have  been 
surprisingly  few.  It  is  a  field  that  should  repay  investi- 
gation, promising  to  afford  a  clearer  insight  into  the 
intermediary  metabolism  in  this  disorder.  One  of  the 
first  to  touch  upon  this  question  was  Garrod,  who  in  1848 
reported  that  there  was  a  diminution  of  potassium  salts 
in  the  urine  and  in  the  blood  of  scurvy  patients.  In  1877 
Ealf  e  confirmed  the  potassium  deficiency  in  the  urine,  but 
denied  its  importance  from  an  etiologic  standpoint,  as  he 
was  unable  to  benefit  scurvy  patients  by  administering 
potassium  nitrate.  He  reported  an  increase  of  uric  acid 
in  the  urine,  a  diminution  of  the  total  acidity,  and  a  reduc- 
tion of  the  alkaline  phosphates.  Litten  found  the  analyses 
of  the  urine  very  contradictory  in  respect  to  potassium, 
but  stated  that  beyond  a  doubt  its  uric  acid  content  is 
increased  at  the  height  of  the  disease,  although  this  dimin- 
ishes rapidly  with  convalescence.  These  few  and  scat- 
tered articles  comprise  the  sum  of  metabolic  studies  up 
to  the  last  decade,  and  even  during  the  succeeding  period 
they  have  been  very  few — so  few,  indeed,  that  they  furnish 
insufficient  data  from  which  to  draw  conclusions. 

The  first  careful  study  of  the  mineral  metabolism  in 
a  case  of  scurvy  is  that  of  Baumann  and  Howard,  pub- 
lished in  1912.  Its  conclusions  are  not  very  definite. 
They  may  be  summed  up  by  their  statement  that  "chlorin 
and  sodium  were  retained  during  the  fruit-juice  period, 
but  excreted  in  excess  of  the  intake  during  the  prelimi- 
nary period,' '  and  that  "more  potassium,  calcium  and 

16  241 


242  SCURVY:    PAST  AND  PRESENT 

magnesium  were  retained  during  the  fruit-juice  period.' ' 
This  same  year  Lust  and  Klocman  published  the  first 
metabolism  study  of  a  case  of  infantile  scurvy.  The  baby 
was  18  months  old  and  the  metabolic  changes  were  investi- 
gated during  the  active,  convalescent,  and  "the  healing 
stage' '  of  the  disorder.  This  study  seems  to  have  been 
carefully  carried  out.  The  fact,  however,  that  the  infant 
received  800  c.c.  daily  of  slightly-boiled  milk  during  the 
active  stage,  and  was  improving  at  this  time,  may  also 
have  had  a  beneficial  effect  on  the  metabolism  in  respect 
to  scurvy.  The  results  of  these  writers  are  surprising — 
quite  different  from  what  they  expected  or  what  we  should 
have  expected.  They  write :  "The  balance  of  the  mineral 
metabolism,  including  the  total  ash,  the  calcium,  phos- 
phorus and  chlorin  during  the  florid  stage  of  the  disease 
must  be  regarded  not  only  as  not  damaged,  compared  to 
that  of  the  healthy  child,  but  indeed  as  somewhat  in- 
creased.' '  "All  the  more  striking,  on  the  contrary,  are 
the  results  found  during  the  stage  of  convalescence.  Here 
the  balances  were  all  markedly  negative,  and  only  after  a 
lapse  of  weeks  was  the  tendency  manifested  to  a  return 
to  normal  conditions."  The  authors  regard  these  results 
as  indicating  a  sort  of  washing  out  of  "dead  material" 
during  convalescence — of  material  which  had  gathered 
during  the  florid  stage  of  the  disease.  According  to  their 
interpretation  the  disease  is  due,  not  to  a  primary  or 
secondary  salt  deficiency,  but  to  a  disturbance  in  salt 
elimination,  and  in  the  first  place,  of  a  calcium  excretion. 
This  is  shown  by  the  fact  that  even  in  the  ' '  stage  of  heal- 
ing, ' '  when  the  total  ash  and  the  phosphorus  balance  once 
more  had  become  positive,  the  calcium  balance  neverthe- 
less remained  somewhat  negative.  The  metabolism  of 
infantile  scurvy,  they  believe,  far  from  showing  a  resem- 


METABOLISM  243 

blance  to  rickets,  manifests  quite  the  contrary  tendency. 
The  study  of  this  case  of  infantile  scurvy  and  that  of 
Baumann  and  Howard  of  a  case  of  adult  scurvy,  com- 
prise the  total  investigation  of  the  metabolism  in 
human  scurvy. 

In  the  course  of  a  recent  discussion  on  rickets  before 
the  Medical  Society  of  Vienna,  Moll  states  briefly  that  in 
a  case  of  infantile  scurvy,  at  the  height  of  the  disease,  he 
found  a  positive  calcium  balance,  which  became  poor  and 
later  negative  on  giving  fruit  juice;  in  other  words,  a 
partial  confirmation  of  the  work  which  has  just  been  cited. 

In  1913  Bahrdt  and  Edelstein  reported  the  analyses  of 
the  organs  of  an  infant  almost  nine  months  old  who  died 
of  scurvy;  an  examination  of  the  tissues,  especially 
of  the  bones,  should  be  most  valuable  in  checking  up 
determinations  of  the  metabolism  during  life.  This  in- 
vestigation runs  absolutely  contrary  to  that  of  Lust  and 
Klocman.  The  bones  showed  a  decrease  of  ash,  especially 
of  calcium  and  of  phosphorus,  and  also  a  lack  of  calcium 
in  the  muscles,  but  normal  amounts  in  the  liver  and  in  the 
kidneys.  These  conditions  resemble  the  deficiency  of  ash 
and  of  lime  commonly  associated  with  rickets,  and  it  seems 
quite  possible  that  this  infant  had  rickets  as  well  as  scurvy, 
and  that  in  this  way  the  discrepancy  between  the  two 
reports  is  to  be  explained.  The  fact  that  the  water  con- 
tent of  the  bones  was  two  to  three  times  the  normal, 
also  lends  emphasis  to  this  interpretation.  In  any  metab- 
olism study  of  infantile  scurvy,  great  care  tvill  have  to  be 
exercised  that  the  disorder  is  not  complicated  by  rickets, 
and  the  issue  thereby  confused.  It  will  be  very  difficult 
to  avoid  this  pitfall,  for  there  is  no  test  by  which  early 
rickets  can  be  diagnosed.  The  danger  of  this  complication 
may  be  realized  when  we  bear  in  mind  that  the  majority 


244  SCURVY:    PAST  AND  PRESENT 

of  infants  have  rickets  to  some  degree.  An  investigation 
of  the  chemistry  of  adult  scurvy  has  an  advantage  from 
this  point  of  view. 

Chemical  examination  of  the  blood  has  yielded  such 
valuable  information  regarding  metabolic  diseases,  that  it 
might  be  expected  to  shed  light  on  the  disturbances  of 
scurvy.  The  only  investigation  from  this  standpoint  is 
that  of  Hess  and  Killian,  who  have  reported  estimations 
of  the  urea,  creatinine,  sugar,  C02  combining  power,  dias- 
tase, cholesterol,  chlorine  and  calcium.1  The  urea  con- 
tent was  normal,  varying  between  12  and  14  mg.  per 
100  c.c.  of  blood;  this  is  the  average  of  twenty-one  tests 
on  ten  cases  of  infantile  scurvy.  [In  severe  cases  of 
beriberi  Yano  and  Nemoti  have  recently  reported  that 
the  blood  contains  an  increase  of  urea,  and  that  its  excre- 
tion is  frequently  disturbed.]  The  creatinine  was  esti- 
mated in  two  cases  and  was  found  to  be  2.0  mg.  and  1.7  mg. 
per  cent.,  respectively, — also  normal  figures.  The  blood 
sugar  varied  from  0.12  to  0.14  per  cent,  and  was  examined 
in  almost  all  the  cases  in  which  urea  was  estimated ;  these 
figures  are  at  the  upper  level  of  normality  (no  attention 
was  paid  to  the  interval  elapsing  between  the  feeding  and 
the  withdrawal  of  the  blood).  The  diastatic  activity  was 
likewise  normal.  The  C02  combining  power  showed  fig- 
ures under  40  to  45,  according  to  the  Van  Slyke  method, 
and  indicated  therefore  a  mild  degree  of  acidosis.  In  six 
cases  the  chlorides  were  estimated,  the  figures  being  re- 
markably constant  at  about  0.42  or  0.43.  Cholesterol  was  a 
little  below  normal  in  the  four  cases  examined.  Contradic- 
tory results  were  obtained  in  regard  to  calcium.  Earlier 
tests  showed  a  definite  deficiency  of  this  salt,  but  those 

1  Almost  all  of  these  cases  were  receiving  liberal  daily  amounts  of  cod 
liver  oil,  which  should  exclude  the  possibility  of  complicating  rickets. 


METABOLISM  245 

carried  out  more  recently  have  generally  yielded  nor- 
mal results.  Further  studies  of  the  blood  calcium  are 
highly  desirable  to  ascertain  whether  it  varies  in  amount 
in  the  circulation,  and  especially  in  different  stages  of  the 
disease.  This  aspect  is  worthy  of  particular  attention 
in  view  of  the  positive  calcium  balance  noted  by  Lust  and 
Klocman  during  the  active  stage  of  scurvy,  and  the  nega- 
tive balance  during  the  period  of  convalescence. 

It  is  evident  from  the  limited  data  concerning  the  blood 
chemistry  of  scurvy  that  it  is  a  field  which  has  been  inade- 
quately explored  and  will  repay  more  intensive  study. 
Investigations  of  this  kind  have  recently  been  made  pos- 
sible by  the  introduction  of  accurate  methods  requiring 
only  small  quantities  of  blood. 

Studies  of  the  metabolism  of  animals  suffering  from 
scurvy  are  almost  as  few  as  those  on  man.  The  work  of 
Morgan  and  Beger,  which  is  frequently  quoted  in  this 
connection,  is  not  applicable,  as  it  concerns  rabbits,  which 
do  not  develop  scurvy.  They  found  that  rabbits  fed  solely 
on  oats  and  water  suffered  in  their  nutrition  (loss  of  appe- 
tite, emaciation,  paralysis  of  hind  legs),  and  could  be 
cured  by  the  addition  of  sodium  bicarbonate  to  the  dietary. 
In  1916  Lewis  and  Karr  published  a  paper  on  the  con- 
stituents of  the  blood  and  the  tissues  of  guinea-pigs  fed 
on  an  exclusive  oat  diet.  They  found  the  urea  content 
several  times  greater  than  normal,  but  that  it  fell  to  nor- 
mal once  more  if  cabbage  or  orange  juice  was  given. 
From  the  standpoint  of  scurvy,  this  investigation  is  open 
to  the  criticism  that  the  diet  was  too  incomplete,  and  also, 
as  the  authors  suggest,  that  the  animals  suffered  from 
partial  starvation  and  a  lack  of  water. 

In  the  following  year  Karr  and  Lewis  published  a 
paper  on  a  different  phase  of  this  subject,  and  came  to  the 


246  SCURVY:    PAST  AND  PRESENT 

following  conclusions:  "No  changes  in  urinary  elimina- 
tion of  phenols,  nor  in  the  degree  of  conjugation  of  the 
phenols,  were  observed,  provided  the  factor  of  partial 
starvation  was  ruled  out.  This  is  believed  to  indicate 
that  no  increased  bacterial  action  occurs  in  the  intestine 
of  scorbutic  guinea-pigs  despite  the  difficulty  of  evacua- 
tion of  the  faeces.' '  These  results  are  in  harmony  with 
the  bacteriological  study  of  Torrey  and  Hess,  who  found 
that  there  was  no  increase  in  the  proteolytic  flora  of 
the  intestine  in  infants  or  in  guinea-pigs  suffering 
from  scurvy. 

In  1917  Bauman  and  Howard  published  the  only  me- 
tabolism study  which  has  been  carried  out  on  guinea-pigs 
suffering  from  scurvy,  and  they  are  of  the  opinion  that 
this  disorder  has  a  profound  effect  on  the  mineral  metab- 
olism of  this  animal.  The  calcium  was  excreted  in  nota- 
bly large  amount;  potassium  was  also  lost,  and  to  a 
greater  extent  than  sodium;  the  only  element  which  was 
consistently  retained  during  the  active  stage  as  well 
as  during  the  period  of  recovery,  was  magnesium.  This 
study  was  followed  shortly  by  one  from  the  same  labora- 
tory, by  Howard  and  Ingvaldsen,  carried  out  on  a  monkey 
suffering  from  scurvy.  It  was  inconclusive,  not  conform- 
ing to  the  experiments  on  the  guinea-pigs;  the  authors 
state  that  the  "changes  in  the  mineral  excretion  of  the 
monkey  during  the  scorbutic  period  were  not  sufficiently 
significant  to  admit  of  easy  interpretation."  "The 
marked  loss  of  the  various  mineral  substances  encoun- 
tered in  experiments  with  man  and  guinea-pig  was  not 
observed  in  the  present  series.' '  It  should  be  remem- 
bered, however,  that  the  diets  of  the  guinea-pigs  and  the 
monkeys  were  quite  different,  the  former  consisting 
mainly  of  oats,  and  the  latter  of  condensed  milk.     It  is 


METABOLISM  247 

quite  possible  that  the  basic  diet  may  play  a  role  in  the 
metabolism  of  this  disease,  although,  as  stated  elsewhere, 
its  effect  cannot  be  noted  clinically.  Special  attention 
should  be  paid  to  this  factor  in  metabolic  studies,  in  view 
of  the  widely-held  opinion  that  the  carbohydrates  exert 
a  potent  influence  in  the  development  of  beriberi. 

The  investigations  of  the  nitrogen  metabolism  in  man 
and  in  animals  have  been  most  unsatisfactory.  The  two 
on  human  beings — an  infant  and  an  adult — were  nega- 
tive; that  on  guinea-pig  scurvy  cannot  be  utilized  on 
account  of  the  restricted  diet  of  oats,  which  contained 
insufficient  nitrogen,  whereas  the  one  on  the  monkey 
showed  some  loss  of  nitrogen,  which  led  the  authors 
to  suggest  an  increased  nitrogenous  catabolism  in  scurvy. 
This  comprises  the  total  data  on  this  subject. 

Summarizing  the  results  of  these  few  metabolic 
studies,  it  may  be  stated  that  they  harmonize  on  one 
point  only — the  positive  balance  of  calcium  during  the 
active  stage  of  the  disease.  The  investigation  of  Bauman 
and  Howard  on  adult  scurvy,  of  Lust  and  Klocman 
and  of  Moll  on  infantile  scurvy,  and  of  Howard  and 
Ingvaldsen  on  the  monkey,  are  all  in  agreement  in  this 
important  conclusion. 


CHAPTER  XI 
RELATION   OF   SCUEVY  TO   OTHER  DISEASES 

In  the  foregoing  there  has  been  frequent  reference 
to  the  close  relationship  between  scurvy  and  the  incidence 
of  the  infectious  diseases — to  the  fact  that  a  scorbutic 
condition  increases  the  susceptibility  to  infection.  This  is 
indeed  one  of  the  most  characteristic,  as  well  as  one  of  the 
most  important  phenomena  associated  with  scurvy  and 
other  disorders  resulting  from  vitamine  deficiency.  Men- 
tion has  been  made  of  the  special  susceptibility  to  the 
diphtheria  bacillus,  and  to  the  organisms  leading  to  coryza 
and  the  respiratory  diseases,  but  no  doubt  this  applies 
also  to  invasion  by  other  bacteria.  We  wish,  however, 
to  confine  ourselves  to  the  nutritional  disorders,  first  in 
their  relationship  one  to  the  other,  and  second,  as  a  group 
of  deficiency  diseases,  due  to  a  lack  of  vitamines  of  various 
kinds.  As  is  well  known,  in  addition  to  scurvy,  this  group 
generally  includes  beriberi,  a  disease  attributed  to  a  lack 
of  the  water-soluble  vitamine,  and  xerophthalmia,  an 
eye  condition  which  recently  has  been  brought  about  in 
rats  by  placing  them  on  a  diet  free  from  fat-soluble  vita- 
mine. These,  however,  form  only  the  nucleus  of  the  dis- 
orders which  commonly  are  included  in  this  category. 
Schaumann,  the  first  to  formulate  this  classification,  illus- 
trated his  conception  of  the  interrelationship  by  depicting 
the  various  members  as  spokes  of  a  wheel  surrounding 
a  central  hub.  He  included  scurvy,  rickets,  osteomalacia, 
typical  beriberi,  ship-beriberi,  pellagra  and  mehlnaer- 
schaden.  Funk  made  a  similar  classification  of  dis- 
orders which  he  termed  the  "avitaminosen."    There  is 

248 


RELATION  TO  OTHER  DISEASES  249 

a  tendency  to  enlarge  rather  than  to  decrease  the  member- 
ship of  this  class,  and  recently  war  or  hunger  edema, 
infantile  atrophy  and  diarrhoea,  sprne,  cceliac  disease, 
leprosy  and  others  have  been  proposed  as  suitable  candi- 
dates. At  the  present  time  it  is  impossible  to  determine 
which  and  how  many  of  this  motley  company  should  be 
associated  with  scurvy.  Some,  possibly,  are  the  result 
of  a  lack  of  vitamine,  but  for  the  present  it  will  be  well 
to  bear  in  mind  that  three  vitamines  only  have  stood  the 
test  of  experiment,  and  only  these  three  therefore  can  be 
definitely  connected  in  a  causal  relationship  with  patho- 
logic conditions.  In  addition  to  this  consideration  of  the 
interrelationship  of  the  ' '  deficiency  diseases, ' '  the  kinship 
of  allied  disorders — more  particularly  of  rickets — must 
be  discussed. 

Although  at  first  thought  beriberi  and  scurvy  would 
seem  far  apart  from  a  clinical  point  of  view,  they  have 
some  important  features  in  common.  In  both  there  is  a 
tendency  to  a  rapidity  of  the  heart 's  action  and  a  marked 
lability  of  the  pulse,  to  an  enlargement  of  the  cardiac 
ventricles,  to  an  involvement  of  the  vagus,  and  to  an 
exaggeration  of  the  deep  reflexes.  It  is  unnecessary  to 
describe  these  signs  and  symptoms  in  detail,  as  they  have 
been  fully  considered  under  symptomatology.  It  has  been 
recorded  from  time  to  time  that  under  certain  circum- 
stances scurvy  has  developed  in  man  where  one  should 
have  expected  beriberi,  and  vice  versa.  Darling,  who  has 
had  a  large  experience  in  this  field,  writes:  "A  deficient 
dietary  in  a  tropical  African  negro  mine  laborer  causes 
severe  scurvy,  in  a  Cape  Colony  African  mine  laborer, 
mild  scurvy,  and  in  some  African  negroes  a  diet  that 
causes  scurvy  in  one  set  of  men  causes  neuritis  in  others. " 
Possibly  some  minor  differences  in  the  dietary  can  ex- 


250  SCURVY:    PAST  AND  PRESENT 

plain  this  difference  in  reaction — for  we  do  not  know  all 
the  sources  of  the  water-soluble  vitamine,  but  such  an 
experience  deserves  to  be  cited  as  it  is  not  an  isolated 
instance.  It  is  all  the  more  worthy  of  attention  because 
it  harmonizes  to  a  certain  extent  with  the  everyday  experi- 
ence of  animal  investigation.  As  has  been  stated  else- 
where, a  diet  of  decorticated  grain  will  lead  to  scurvy  in 
the  guinea-pig,  to  polyneuritis  in  the  pigeon,  and  to  a 
combination  of  these  diseases  in  the  hog !  Results  of  this 
kind  show  that  there  must  be  a  relationship  between  the 
etiologic  factors  of  scurvy  and  of  beriberi.  It  is  unwise 
at  present  to  attempt  to  define  the  relationship  more 
precisely.  The  remarkable  observation,  first  made  by 
Fuerst,  and  since  confirmed  by  numerous  investigators, 
that  seeds  and  legumes  are  devoid  of  antiscorbutic  potency 
but  acquire  this  power  on  sprouting,  constitutes  another 
link  in  the  evidence  of  their  kinship.  Funk  has  suggested 
that  the  antiscorbutic  vitamine  can  be  formed  from  the 
"antineuritic"  vitamine,  a  theory  which  is  very  attrac- 
tive but  needs  confirmation  and  experimental  proof.  It 
is  quite  evident  that  this  change  does  not  usually  occur 
in  animals,  in  view  of  the  specificity  of  the  vitamines  for 
their  respective  diseases — of  the  antiscorbutic  for  scurvy 
and  the  water-soluble  for  beriberi. 

It  will  be  noted  that  "ship-beriberi"  is  included  in 
this  group  of  diseases.  Very  little  is  known  about  this 
condition,  except  what  is  contained  in  the  investigation 
of  Nocht  (1903)  and  that  of  Hoist  and  Froelich.  It  is  a 
very  rare  condition  but  of  interest  because  it  is  charac- 
terized by  spongy,  hemorrhagic  gums  and  other  signs 
encountered  in  scurvy.  The  feature  which  differentiates 
it  sharply  from  scurvy,  however,  is  an  anaesthesia  of  the 
extremities.     Ship-beriberi  is  generally  regarded  as  a 


RELATION  TO  OTHER  DISEASES  251 

combination  of  beriberi  and  scurvy.  Where  these  two  dis- 
orders occur  concomitantly,  the  beriberi  manifests  itself 
some  months  before  the  scurvy,  as  the  latter  takes  much 
longer  to  develop. 

In  considering  the  vitamines  in  connection  with  dis- 
eases of  the  nervous  system,  mention  may  be  made  of 
"central  neuritis"  and  the  "peripheral  neuritis"  which 
has  been  reported  from  the  West  Indies.  This  bears  only 
a  partial,  resemblance  to  beriberi,  as  there  is  no  edema, 
nor  dyspnoea,  and  its  course  is  more  chronic.  Judging 
from  the  report  of  Edwards  from  Jamaica,  the  cases  more 
closely  resemble  pellagra,  terminating  after  many  years. 
A  degeneration  of  the  cells  of  the  spinal  cord  was  found 
and  "in  some  isolated  patches  of  the  cerebellum  and  in 
the  roots  of  the  optic  and  auditory  nerves."  The  disease 
occurs  among  the  poor  classes  whose  diet  is  inadequate 
chiefly  in  nitrogen. 

Eijkman  was  the  first  to  draw  an  analogy  between 
beriberi  and  'pellagra,  and  thus  to  suggest  that  the  latter 
might  be  a  disease  due  to  an  unidentified  factor;  he  com- 
pared the  pernicious  effect  of  a  diet  of  polished  rice  with 
that  of  decorticated  corn.  Of  recent  years,  largely  as  the 
result  of  the  investigations  of  Goldberger  and  his  co- 
workers, pellagra  has  come  to  be  regarded  as  a  dietetic 
disorder  primarily  due  to  a  lack  of  adequate  protein, 
rather  than  to  a  lack  of  a  specific  vitamine.  Its  relation- 
ship to  scurvy  cannot,  therefore,  at  the  present  time,  be 
discussed  from  an  etiologic  viewpoint.  Apart,  however, 
from  the  question  of  etiology,  the  two  diseases  have  cer- 
tain clinical  symptoms  in  common.  Weston  states  that 
"  distinguished  physicians,  who  were  really  astute  ob- 
servers, have  mistaken  pellagra  for  scurvy,  eczema, 
various  kinds  of  intestinal  troubles,  syphilis,  and  many 


252  SCURVY:    PAST  AND  PRESENT 

other  diseases.' '  In  the  chapter  on  symptomatology, 
attention  has  been  directed  to  the  fact  that  an  eczema 
which  yields  to  antiscorbutic  treatment  may  occur  in 
scurvy ;  at  times  it  presents  the  symmetrical  arrangement 
so  typical  of  pellagra.  In  other  cases  a  fleeting  erythema 
may  be  observed,  another  sign  noted  frequently  in  pella- 
grins. In  some  instances  congestion  of  the  gums  has 
been  recorded.  In  describing  a  little  girl  of  three  who 
had  pellagra,  Weston  writes :  '  *  The  gums  are  also  red 
and  swollen,  suggesting  scurvy.' '  This  child  had  eaten 
large  amounts  of  turnips,  so  that  there  could  have  been 
no  question  of  complicating  scurvy.  Lombroso  and  some 
of  the  earlier  authors  drew  attention  to  the  fact  that 
fragility  of  the  bones,  of  the  ribs  and  of  the  long  bones, 
was  often  associated  with  pellagra.  These  various  clini- 
cal similarities  should  not  be  construed  as  evidence  in 
favor  of  the  ' '  avitamine '  '  nature  of  pellagra.  They  indi- 
cate, rather,  that  in  nutritional  disorders,  whatever  may 
be  their  underlying  cause,  the  vessels,  the  bones,  and  other 
tissues  may  suffer  and  lead  to  similar — but  not  identical — 
clinical  pictures.1 

The  relation  between  scurvy  and  rickets  is  a  subject 
which  was  discussed  by  Glisson.  With  the  renewed  inter- 
est in  infantile  scurvy  which  followed  Barlow's  work 
toward  the  end  of  the  last  century,  children's  specialists 
ranged  themselves  into  opposing  camps  on  the  question 
of  the  interrelationship  and  interdependence  of  these  two 

1  There  is  no  adequate  reason  for  placing  in  this  group  "  coeliac  dis- 
ease," a  nutritional  disorder  of  children  recently  described  by  Still,  and 
suggested  by  McCarrison  as  belonging  to  the  category  of  the  vitamine  de- 
ficiency diseases.  A  case  of  this  kind  has  come  to  our  attention  which 
resembled  pellagra  in  many  respects.  It  showed  the  bright  red,  denuded 
tongue,  the  intestinal  symptoms,  the  occasional  edema,  marked  loss  in 
weight,  and  evanescent  erythema — all  symptoms  of  markedly  disturbed  nu- 
trition but  not  distinctive  of  a  lack  of  vitamines. 


RELATION  TO  OTHER  DISEASES  253 

diseases.  Some  accepted  Barlow's  dictum  that  infantile 
scurvy  is  an  absolutely  distinct  and  separate  entity; 
others,  for  example,  Hirschsprung,  declared  that  the  so- 
called  scurvy  was  merely  a  form  of  rickets;  whereas  a 
third  group  considered  it  a  combination  of  rickets  and 
scurvy.  This  last  viewpoint  was  actively  maintained  by 
Cheadle  on  the  clinical  side,  and  later  by  Schoedel  and 
Nauwerk  on  the  pathologic  side — the  latter  declaring  that 
rickets  is  "an  inseparable  component  of  infantile  scurvy/ * 
and  that  the  entire  disease  should  be  regarded  merely 
as  "an  episode  in  the  course  of  rickets.,,  Even  Barlow, 
in  a  paper  published  in  1894,  wrote:  "Rhachitic  changes 
already  present  may  act  as  a  physiological  determinant 
of  the  sites  in  which  scurvy  becomes  manifest,,  and 
"rickets  as  a  basis  plus  inadequate  food  gives  the  sim- 
plest explanation  of  the  typical  case"  (of  scurvy). 

We  had  an  exceptional  opportunity  to  test  this  thesis 
in  1914,  in  an  institution  where  scurvy  broke  out  among 
infants  who  were  on  a  diet  of  pasteurized  milk.  All  these 
infants  were  receiving  cod  liver  oil  daily,  as  prophylactic 
treatment  against  rickets.  Many  infants  have  been  seen 
since  that  time,  who  in  spite  of  receiving  cod  liver  oil 
developed  scurvy,  and  others  in  whom  large  doses  of 
this  oil  failed  to  mitigate  the  scurvy,  although  it  pre- 
vented rickets.  The  same  failure  has  been  encountered 
in  the  treatment  of  scurvy  in  guinea-pigs.  This  experi- 
ence has  been  without  exception,  both  from  a  prophy- 
lactic and  a  curative  standpoint. 

Confusion  between  the  two  diseases  has  resulted  from 
the  fact  that  the  majority  of  infants  in  the  Temperate 
Zone  have  some  degree  of  rickets.  Thus  the  two  diseases 
have  been  found  very  frequently  associated  in  pathologic 
examination  of  the  bones,  leading  some  to  infer  that  they 


254  SCURVY:    PAST  AND  PRESENT 

are  in  some  way  interdependent.  They  have  been  also 
confused  clinically,  as  mentioned  in  another  connection, 
owing  to  the  fact  that  beading  of  the  ribs — the  rhachitic 
rosary — has  been  mistakenly  regarded  as  a  pathognomonic 
sign  of  rickets,  whereas  it  is  also  a  sign  common  to  scurvy. 
It  is  important  to  bear  in  mind  that  from  the  pathologic 
viewpoint  scurvy  and  rickets  present  strikingly  dissimilar 
pictures — the  former  is  characterized  by  an  almost  com- 
plete cessation  of  activity  of  bone-forming  elements, 
whereas  the  latter  is  distinguished  by  a  hyperplastic  con- 
dition leading  to  a  marked  overgrowth  of  cartilage  and 
of  abnormal  bone.  Viewed  from  the  pathologic,  etiologic 
and  clinical  standpoint,  we  believe  that  there  is  no  basis 
for  assuming  an  interrelationship  between  the  two  dis- 
orders, and  that  scurvy  will  develop  as  readily  and  as 
rapidly  where  rickets  is  absent  as  where  it  is  present.2 

It  is  premature  to  discuss  the  relationship  of  these  two 
disorders  from  the  vitamine  standpoint.  In  1910 
Schaumann  suggested  that  rickets  was  due  to  a  lack  of 
a  specific  food  factor,  and  somewhat  later  Funk  included 
it  among  the  "avitaminosen."  Recently  Mellanby,  as 
the  result  of  experiments  on  dogs,  has  affirmed  that  the 
fault  lies  in  a  lack  of  the  fat-soluble  or  a  closely-related 
vitamine.  Investigations  of  the  near  future  will  probably 
decide  the  merits  of  this  contention ;  our  experience  is  that 
rickets  develops  in  infants  even  where  the  diet  contains 
adequate  fat-soluble  vitamine.  If  rickets  is  proved  to 
be  a  disorder  depending  on  a  vitamine,  it  belongs,  natu- 

2  The  only  evidence  in  favor  of  a  true  interrelationship  is  furnished  by 
a  necropsy  report  of  Hart  ami  Lessing  on  one  of  five  monkeys  fed  on  a 
scorbutic  diet.  This  animal  died  of  disseminated  tuberculosis,  and  the 
\)<>wh  showed  "the  '-lassie  picture  of  severe  rickets."  This  occurrence  can- 
not he  explained,  although  illness  and  lack  of  exercise  no  doubt  played  a 
role.  Until  similar  cases  are  reported,  the  incident  must  be  regarded  merely 
as  interesting  and  suggestive. 


RELATION  TO  OTHER  DISEASES  255 

rally,  in  the  same  group  as  scurvy.  This  would  indicate 
relationship,  but  not  interrelationship.  Just  as  the  mere 
fact  that  a  lack  of  vitamines  leads  to  scurvy  and  to  beri- 
beri does  not  signify,  in  theory  or  in  practice,  the  exist- 
ence of  pathogenetic  interrelationship.  However,  as 
stated,  this  is  a  subject  which  does  not  as  yet  rest  on  a 
secure  foundation. 

Osteogenesis  imperfecta  and  osteomalacia  are  dis- 
orders of  dietetic  or  metabolic  origin  characterized  by 
fragility  of  the  bones.  The  latter  has  developed  new  sig- 
nificance and  importance  due  to  its  increased  occurrence 
in  almost  epidemic  form  in  the  Central  Empires  at  the 
close  of  the  World  War.  The  etiology  of  both  disorders  is 
most  obscure.  In  the  future  in  considering  their  patho- 
genesis it  will  be  well  to  draw  a  sharp  distinction  between 
them.  Osteogenesis  imperfecta  is  a  disease  in  which  an 
injury  occurs  to  the  foetus  without  any  manifest  illness  in 
the  mother,  which  seems  to  indicate  a  primary  lesion  of  the 
foetus  (perhaps  metabolic) ;  osteomalacia,  on  the  other 
hand,  attacks  the  mother  who  gives  birth  to  an  apparently 
healthy  foetus.  The  latter  gains  added  interest  because 
it  is  a  disease  of  the  bones  which  is  attributed  to  dys- 
function of  the  endocrine  glands,  to  a  disturbance  espe- 
cially of  the  parathyroid.  If  this  observation  is  confirmed, 
it  furnishes  another  anatomical  basis  for  associating 
the  glands  of  internal  secretion  with  pathologic  conditions 
of  the  bones. 

One  cannot  survey  the  various  diseases  of  the  bones — 
scurvy,  rickets,  osteoporosis,  osteogenesis  imperfecta, 
osteomalacia,  etc., — without  realizing  that  this  group  is  at 
present  in  a  state  of  great  confusion  and  will  have  to  be 
rearranged  and  winnowed.  The  differentiation  between 
some  of  these  diseases  is  not  in  every  instance  clear  mor- 


256  SCURVY:    PAST  AND  PRESENT 

phologically — for  instance,  early  cases  of  scurvy  and 
osteoporosis — so  that  it  is  difficult  to  consider  them 
satisfactorily  from  the  standpoint  of  pathogenesis.  Clini- 
cal differentiation  is  still  more  difficult  and  uncertain.  It 
seems  probable  that  new  entities  will  be  established,  as 
has  happened  in  the  past.  It  is  not  so  long  since  rickets 
included  almost  all  the  bone  diseases  of  infants.  Grad- 
ually congenital  syphilis,  scurvy,  and  achondroplasia 
were  segregated  as  distinct  diseases.  Probably  a  similar 
separation  of  other  pathologic  conditions,  now  so  en- 
tangled as  to  be  indistinguishable,  will  be  evolved. 

Among  the  diseases  which  have  been  attributed  to  a 
vitamine  deficiency  are  "war  or  hunger  edema, "  sprue, 
the  "mehlnaerschaden"  of  infants,  and  the  "exudative 
diathesis"  described  by  Czerhy  and  Keller.  Future  in- 
vestigation will  disclose  whether  any  of  these  disorders 
belong  in  the  group  with  scurvy.  The  hunger  edema, 
noted  in  the  late  war  and  in  previous  wars,  seems  to  be 
a  complex  condition,  quite  dissociated  from  scurvy,  as 
many  of  the  sufferers  consumed  comparatively  large 
quantities  of  potatoes  or  other  vegetables.  The  "mehl- 
naerschaden"  resembles  scurvy  and  the  other  vitamine 
disorders  in  its  tendency  to  produce  hydremia  and  sus- 
ceptibility to  infection.  It  also  develops  in  spite  of  a 
liberal  supply  of  antiscorbutic  foodstuff  in  the  dietary. 
As  its  name  implies,  it  comes  about  on  a  diet  containing 
large  quantities  of  carbohydrate,  of  the  cereal  paps  so 
commonly  fed  to  infants.  It  is  conceivable  that  an  un- 
balanced diet  of  this  kind  may  not  provide  a  sufficiency  of 
all  the  vitamines. 

It  does  not  seem  probable  that  exudative  diathesis,  a 
term  which  implies  a  predisposition  to  develop  exudations 
or  denudations  of  the  skin  and  mucous  membranes,  is  the 


RELATION  TO  OTHER  DISEASES  257 

result  of  a  lack  of  vitamine.  This  condition  does,  how- 
ever, predispose  to  scurvy.  The  association  was  very 
evident  in  the  group  of  cases  reported  by  Hess  and  Fish 
in  1914.  It  is  not  without  significance  that  the  blood- 
vessels in  exudative  diathesis  also  show  a  decided  weak- 
ness, an  increased  permeability,  as  judged  by  the  ' '  capil- 
lary resistance  test."  In  both  scurvy  and  in  exu- 
dative diathesis  eczema  and  petechial  hemorrhages 
are  encountered. 

There  may  be  nutritional  diseases  due  to  an  excess  of 
food  rather  than  to  a  deficiency.  A  superfluity  may  be 
harmful  by  hindering  the  proper  utilization  of  the  food, 
or  may  possibly  lead  to  the  formation  of  deleterious  prod- 
ucts. Disturbances  of  this  kind  do  occur.  For  example, 
it  is  by  no  means  uncommon  for  an  infant  which  has  been 
overfed  with  milk  to  show  the  typical  signs  of  rickets. 
Young  guinea-pigs  which  are  fed  liberal  amounts  of  cow's 
milk  develop  a  disease  characterized  by  fragility  of  the 
bones.  The  experience  of  Lubarsch,  who  produced  osteo- 
genesis imperfecta  in  rabbits  by  means  of  a  diet  consist- 
ing mainly  of  liver,  or  adrenal  gland,  is  of  interest, 
especially  as  this  condition  did  not  come  about  when  they 
were  fed  muscle  tissue. 

From  what  has  been  stated,  it  must  be  evident  that  this 
subject  not  only  is  in  a  state  of  flux  but  that  it  is  in  a 
state  of  great  confusion.  This  applies  not  only  to  the 
relationship  of  vitamines  to  these  disorders,  but  to  their 
identification  and  demarcation  pathologically  as  well  as 
clinically.  During  the  past  few  years  we  have  begun 
to  regard  these  diseases  from  a  new  viewpoint,  which  no 
doubt  will  be  helpful,  but  it  is  probable  that  they  will 
not  be  sharply  defined  and  their  relationships  determined 
until  it  is  possible  to  bring  about  each  disease  definitely 
17 


258  SCURVY:    PAST  AND  PRESENT 

and  regularly  in  an  experimental  animal.  Until  this  time 
we  should  proceed  slowly,  and  not  bring  about  "con- 
fusion worse  confounded"  by  yielding  to  the  vogue,  and 
grouping  together  heterogeneous  and  little-understood 
clinical  conditions  under  the  caption  of  deficiency  dis- 
eases. There  is  a  growing  danger  of  attributing  every 
unexplained  nutritional  disorder  to  the  new,  overworked, 
but  ill-defined  vitamines — of  their  sharing  with  the  secre- 
tions of  the  endocrine  glands  the  fate  of  becoming  the 
dumping-ground  for  every  unidentified  disorder. 


APPENDIX 

Extract  from  "  Treatise  on  Scurvy,"  by  James  Lind,  London,  1772. 
(a)  Recipe  for  preparing  a  stable  orange  or  lemon  juice.  Let  the 
squeezed  juice  of  these  fruits  be  well  cleared  from  the  pulp  and  purified  by 
standing  for  some  time;  then  poured  off  from  the  gross  sediment;  or,  to 
have  it  still  purer,  it  may  be  filtrated.  Let  it  then  be  put  into  any  clean 
open  vessel  of  china  or  stone-ware,  which  should  be  wider  at  the  top  than 
bottom,  so  that  there  may  be  the  largest  surface  above  to  favor  the  evapor- 
ation. For  this  purpose  a  china  basin  or  punch-bowl  is  proper,  and  gen- 
erally made  in  the  form  required;  all  earthen  glazed  vessels  are  unfit,  as 
their  glazing  will  be  dissolved  by  the  acid.  Into  this  pour  the  purified  juice, 
and  put  it  into  a  pan  of  water,  upon  a  clear  fire.  Let  the  water  come  almost 
to  a  boil,  and  continue  nearly  in  that  state  (with  the  basin  containing  the 
juice  in  the  middle  of  it)  until  the  juice  is  found  to  be  of  the  consistence  of 
a  thick  syrup  when  cold.  The  slower  the  evaporation  of  the  juice  the  bet- 
ter; and  it  will  require  at  least  twelve  or  fourteen  hours  continuance  in 
the  bath  heat  before  it  is  reduced  to  a  proper  consistence. 

It  is  then,  when  cold,  to  be  corked  up  in  a  bottle  for  use.  Two  dozen 
good  oranges,  weighing  five  pounds  four  ounces,  will  yield  one  pound  nine 
ounces  and  a  half  of  pure  juice;  and  when  evaporated,  there  will  remain 
about  five  ounces  of  rob,  or  extract ;  which  in  bulk  will  be  equal  to  less  than 
three  ounces  of  water.  So  that  thus  the  acid,  and  the  virtues  of  twelve 
dozen  lemons  or  oranges,  may  be  put  into  a  quart  bottle,  and  preserved 
for  several  years. 

I  have  now  some  extract  of  lemons  which  was  made  four  years  ago. 

Those  who  intend  this  extract  for  making  punch  may  infuse  some  of  the 
fresh  peel  of  the  oranges  or  lemons  into  the  spirit  before  it  is  used. 

But  for  this  purpose  I  find  it  is  sufficient  to  add  a  very  small  quantity 
of  the  outer  peel  to  the  extract  a  little  before  it  is  taken  off  the  fire,  and 
there  will  be  all  that  is  requisite  to  make  it  entirely  equal  to  the 
freshest  fruit. 

(b)  How  to  preserve  berries  and  other  fruits  for  long  periods.  And 
it  may  be  proper  to  acquaint  them  that  most  berries,  and  several  fruits,  when 
gathered  two-thirds  ripe  on  a  dry  day,  while  the  sun  shines,  if  put  into 
earthen  pots,  or  rather  in  dry  bottles,  well  corked,  and  sealed  up,  so  that 
no  air  or  moisture  can  enter,  will  keep  a  long  time,  and  at  the  end  of  a  year, 
be  as  fresh  as  when  new  pulled. 

(c)  Method  of  preparing  an  antiscorbutic  decoction  from  fir-tops,  leaves, 

259 


260  SCURVY:    PAST  AND  PRESENT 

bark,  etc.  When  the  Swedes  carried  on  a  war  against  the  Muscovites,  almost 
all  the  soldiers  of  their  army  were  destroyed  by  the  scurvy,  having  putrid 
gums,  rigid  tendons,  etc.  But  a  stop  was  put  to  the  progress  of  this  disease 
by  the  advice  of  Erbenius,  the  King's  physician,  with  a  simple  decoction  of 
fir-tops,  by  which  the  most  deplorable  cases  were  perfectly  recovered,  and 
the  rest  of  the  soldiers  prevented  from  falling  into  it. 

I  am  inclined  to  believe  by  the  description  given  by  Cartier  of  the 
ameda  tree,  with  a  decoction  of  the  bark  and  leaves  of  which  his  men  were 
so  speedily  recovered,  that  it  was  the  large  swampy  American  spruce  tree. 

A  simple  decoction  of  the  tops,  cones,  leaves  or  even  green  bark  and 
wood  of  these  trees  is  an  excellent  antiscorbutic  medicine;  but  it  will,  I 
am  apt  to  think,  become  much  more  so  when  fermented,  as  in  making  spruce 
beer.  By  carrying  a  few  bags  of  spruce  or  its  extract  to  sea,  this  whole- 
some drink  may  be  prepared  at  any  time.  But  where  it  cannot  be  had  the 
common  fir-tops  used  for  fuel  in  the  ship  should  be  first  boiled  in  water, 
and  the  decoction  afterwards  fermented  with  molasses  in  the  common 
method  of  making  spruce  beer;  to  which  a  small  quantity  of  wormwood 
and  horse-radish  root  (which  it  is  easy  to  preserve  fresh  at  sea)  may  be 
added.  The  juice  of  the  cocoanut  tree  was  experienced  to  be  of  very  great 
benefit  to  several  persons  afflicted  with  the  scurvy. 


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INDEX 


Acid,  effect  on  keeping  qualities  of 

antiscorbutics,  66,  161 
Acidosis,  244 

theory,  24 
Adrenals,  102 

in  guinea-pig  scurvy,  122 
Adult,  scurvy  in,  history  of,  1 
Age  incidence,  51 

Aging,  effect  on  antiscorbutics  of,  67 
Agglutinins,  effect  of  scurvy  on,  68 
Alimentary  tract,  gross  pathology,  89 
microscopic  pathology,  100 
Alkalization,  effect  on  milk  of,  50 

on  orange  juice  of,  66,  154 
Amboceptor,  effect  of  scurvy  on,  68 
Anasarca,  86,  196 
Animals,  scurvy  in,  114 
Anorexia,  206 

Antiscorbutics,    and    antiscorbutic 
foods,  143,  149,  157 

history  of  use  of,  9,  143 
Antitoxin,  effect  of  scurvy  on,  68 
Appendicitis,  confused  diagnosis,  183 
Appetite,  206 

Apple,  antiscorbutic  value  of,  158 
Armies,  scurvy  in,  3,  15 
Army,   use   of   canned   tomatoes   in 
ration  of  U.  S.,  231 

B 

Bacteria,  fecal,  in  scurvy,  28 

as  etiological  factor  in  scurvy, 

134 
in  tissues,  133 

Bacterial  theory  of  scurvy,  30 

Banana,  antiscorbutic  value  of,  158 

Beading  of  ribs,  197 

in  guinea-pig,  129,  137 
pathology  of,  94 

Beans,  germinated,  167,  231 

Beef  juice,  236 

Beer,  antiscorbutic  value  of,  20,  169 

Beriberi,  differential  diagnosis,  221 
relation  to  scurvy,  249 

Berries,  antiscorbutic  value  of,  156 

Blindness,  182 

Blood  cells,  changes  in,  209-211 


Blood  cells,  chemistry  of,  244,  245 

coagulability  of,  211 
Blood  vessels,  changes  in,  68,  98,  209 
in  guinea  pigs, 
133 
Blood,  vitamine  content  of,  76 
Bones,  gross  pathology,  93 

microscopic  pathology,  105 
Brain,  pathology,  93 
Breast  fed,  scurvy  in,  35 

C 

Cabbage,  antiscorbutic  value  of,  159 

dehydrated,  165 

effect  of  heat  on,  159 
Calcium,  deposits  of,  98,  102,  103 

metabolism,  241-247 
"Capillary  resistance  test,"  212,  257 
Carbohydrates,  34,  59 
" Cardio-respiratory  syndrome,"  200 
Cardiovascular  system,  199 
Carrots,  antiscorbutic  value  of,  159, 

160 
Central  nervous  system,  gross  pathol- 
ogy, 93 
microscopic   pathologv, 
104 
Cereals,  antiscorbutic  value  of,  170 

germinated,  167 
Cerebrospinal  fluid,  203 
Chlorides,  242-247 
Citric  acid  theory,  23 
Climate,  55 

Complement,  effect  of  scurvy  on,  69 
Complexion,  characteristic  change  in, 

176,  184 
Complications  of  scurvy,    182,   202, 

205,  217 
Constipation,  27,  118-122,  207 
Cord,  spinal,  pathology,  93,  104 
Creatinine,  244 
Cure,  236 

D 
Death,  causes  of,  179,  227 
Deficiency   diseases,   general   discus- 
sion, 63,  248 

275 


276 


INDEX 


Diagnosis,  176,  219 
Diastase,  blood  content  of,  244 
Diet,  general,  59 
Digestive  disturbances,  78 
Diphtheria,  antitoxin  in  blood,  68 
as  complication  of  scurvy,  217 
Drying,  effect  on  vitamines  of,  66 
Duodenum,  pathology,  89 
Dysentery,  59,  182 

E 

Economic  status,  55 
Eczema,  195 
Edema,  178,  184,  196 
hunger,  256 
war,  256 
Eggs,  antiscorbutic  value  of,  168 
Endocrine  organs,  gross  pathology,  92 
microscopic  pathology,  104 
extracts   of,   as  preventive, 
172 
theory  of  vitamine  action,  72 
Epidemics,  2,  217 

Epiphyses,  separation  of,  96,  181,  198 
Etiology,  35 

exciting  factors  in,  60 
Excretion  of  vitamine,  77 
Expeditions,  scurvy  in  Arctic,  10 
Experimental  scurvy,  111 
pathogenesis,  116 
pathology,  122 
symptoms,  135 
Exudative  diathesis,  59,  256 
Eyeball,  proptosis,  193 

F 

Familial  tendency,  58 

Fats,  in  diet,  effect  on  scurvy,  59 

Fever,  181,  216 

Foetus,  effect  of  scorbutic  diet  on,  125 

Food,  excess  of,  257 

Foods,  antiscorbutic,  143,  149 

proprietary,  49 
Fractures,  95 
Frost-bite,  180 
Fruit  juices,*  153 
Fruits,  fresh,  144 

G 

Generative  organs,  pathology,  104 
Glands,  endocrine,  72 

changes  in,  73,  92,  104 
Glucose,  blood  content  of,  244 


Grapes,  antiscorbutic  value  of,  158 
Growth  in  scurvy,  213 
Guinea-pig  scurvy,  112,  114 
Guinea-pig  pathogenesis,  116 
pathology,  122 
relation  to  human,  115 
symptoms,  135 
Gums,  177,  181,  184 

in  infantile  scurvy,  189 
pathology  of,  89,  100 

H 

Hair,  changes  in,  194 
Heart,  200 

gross  pathology,  87 

microscopic  pathology,  99 
Heat,  effect  on  vitamine  of,  65 
Hemorrhages,  180,  189 

as  early  symptoms,  178 

distribution  of,  84 

gastric,  208 

orbital,  193 

subperiosteal,  95,  191 

urinary,  204 
History  of  scurvy,  1 
Hog,  effect  of  scorbutic  diet  on,  115 
Hypophysis,  104 


Infantile  scurvy,  history,  10 
in  artificially  fed,  40 
in  breast  fed,  35 
increase  during  World  War,, 

21-22 
relation  to  epidemic  scurvy 

of  adults,  15,  37 
relation  to  rickets,  11,  110, 

252 
symptomatology,  183 
Infection,  as  exciting  factor,  60,  218 
increased  liability  to,  68 
effect  on  prognosis,  227 
Intestines,  gross  pathology,  90 

microscopic  pathology,  100 
Intravenous  use  of  orange  juice,  238 
Irregularities  in  course  of  deficiency 
diseases,  78 


Jaundice,  208 
Joints,  lesions  of,  199 


INDEX 


277 


K 

Kidneys,  gross  pathology,  91 
microscopic  pathology,  102 


Latent  scurvy,  179,  183,  187 
Laxatives,  failure  to  cure  with,  28,  207 
Lemon  juice,  antiscorbutic  value  of, 
153,  234 
dried,  155,  232 
ration  in  British  Navy,  9, 
144 
Lentils,  value  as  antiscorbutic,  167, 

231 
Lice,  theory  of  transmission  of  scurvy 

by,  30 
Lime  juice,  antiscorbutic  value  of,  156 
fallacy  in  regard  to,  149 
use  in  British  Navy,  144 
Liver,  gross  pathology,  91 

microscopic  pathology,  101 
Lungs,  gross  pathology,  88 

microscopic  pathology,  99 
Lymphnodes,  gross  pathology,  92 
microscopic  pathology,  101 

M 

Malnutrition,  general,  58 
Malt  soup,  50 
Marrow,  changes  in,  107 
Meat,  fresh,  147,  168 

salt,  146 
"Mehlnaerschaden"  of  Czerny,  256 
Metabolism  in  scurvy,  241-247 
Milk,  alkalized,  50 

amount    necessary    to    prevent 

scurvy,  49,  117,  150 
boiled,  44,  65 
condensed,  48 
dried,  46,  66,  152 
effect  of  industrial  methods  on, 

43 
evaporated,  45 
pasteurized,  40,  65 

home  vs.  commercial,  42 
sterilized,  44 

breast,  amount  necessary  to  pre- 
vent scurvy,  36,  39,  153 
as  cause  of  beriberi,  39 
cows,  antiscorbutic  value  of,  40, 

152 
goats,  antiscorbutic  value  of,  153 
Mineral  metabolism  in  scurvy,  241- 
247 


Monkey,  scurvy  in,  114,  127 

pathology,  128 
Muscles,  pathology,  97 

N 
Nails,  changes  in,  194 
Necropsy  reports,  82 
Nephritis,  205 

Nerves,    peripheral,     in     guinea-pig 
scurvy,  132 
pathology,  105 
Nervous  system,  effect  of  scurvy  on, 

202 
Nutrition,  general,  in  scurvy,  58,  59, 

213 
Nyctalopia,  182 

O 

Orange  juice,  antiscorbutic  value  of, 
153,  234 
"artificial,"  33 
dried,  155 

effect  of  alkalization  of,  154 
intravenous  use  of,  238 
subcutaneous  use  of,  155 
peel,  antiscorbutic  value  of,  234 
Osteogenesis  imperfecta,  255 
Osteomalacia,  differentiation  of,  from 

scurvy,  255 
Osteomyelitis,  differentiation  of,  from 

scurvy,  222 
Osteoporosis,  differentiation  of,  from 

scurvy,  255 
Osteotabes  infantum,  109 


Pains,  as  early  symptom,  176 
Pancreas,  gross  pathology,  91 

microscopic  pathology,  104 
Pasteurized  milk,  40 
Pathogenesis  of  scurvy,  theories  of, 

23 
Pathology  of  scurvy  in  guinea-pig,  122 
in  man,  gross,  83 

microscopic,  96 
in  monkey,  128 
Peas,  antiscorbutic  value  of,  167,  231 
Pellagra,  251 
Phenols,  excretion  of,  245 
Phosphate  metabolism,  241-247 
Pigeon,  effect  of  scorbutic  diet  on,  114 
Pneumonia,  202 

Posture,  characteristic,  in  guinea-pig, 
136 


278 


INDEX 


Posture,  characteristic,  infant,  183 
Potassium  deficiency  theory,  23 

metabolism,  241-247 
Potatoes,  antiscorbutic  value  of,  6,  7, 

146,  161,  235 
Prevention  of  scurvy,  230 
Prognosis,  225 

Protein  in  diet,  effect  on  scurvy,  59 
Psychic  element  in  scurvy,  57 
Pulse,  181,  201 
Pulses,  germinated,  167,  231 
Purpura,  differential  diagnosis,  221 
Pyorrhea,  relation  to  lesion  of  gums, 

181 

R 

Racial  immunity,  56 

Rats,  effect  of  scorbutic  diet  on,  114, 

115 
Recurrent  scurvy,  228 
Respirations,  201 
Retma,  hemorrhages  in,  105 
Rheumatism,  confusion  with  scurvy, 

176,  220 
Ribs,  beading  of,  197 
pathology,  94 

in  guinea-pig,  129,  137 
Rickets,  relation  of,  to  scurvy,   11, 

110,  252 
Rosary,  94,  197 

S 

Sauerkraut,   antiscorbutic   value   of, 

145 
Season,  effect  on  incidence,  54 
Sex,  effect  on  incidence,  56 
Shaking,effect  on  antiscorbutic  factor, 

68 
Ship  beriberi,  250 
Skin,  pathology,  96 
Spleen,  gross  pathology,  91 

microscopic  pathology,  102 
Sprue,  256 

Starvation,  pathology  of,  125 
Stomach,  gross  pathology,  89 

microscopic  pathology,  100 
Storage  of  vitamine  in  body,  74 
Streptococcus  in  blood  in  scurvy,  134 
Subacute  form  of  scurvy,  184 
Subcutaneous  use  of  antiscorbutics, 

155 
Swede,  antiscorbutic  value  of,   162, 

235 


Symptomatology,  in  adult,  176 

in  infant,  183 
Syphilis,  congenital,  differential  diag- 
nosis, 222,  223 


Teeth,  in  guinea-pig  scurvy,  130,  137 

in  human  scurvy,  177 
Temperature,  in  guinea-pig  scurvy, 
141 
in  human  scurvy,  181,  216 
Thymus,  pathology  of,  104 

use  of  gland  in  treatment,  172 
Thyroid,  pathology  of,  104 

use  of  gland  in  treatment,  172 
Tomatoes,      canned,      antiscorbutic 
value  of,  166,  231,  234 
in  U.  S.  Army  ration,  231 
Toxic    theory    of    pathogenesis    of 

scurvy,  25 
Treatment  of  scurvy,  230 
duration  of,  237 
non-dietetic,  239 

U 

Ultra-violet  rays,  effect  on  antiscor- 
butics, 67 
Urea  content  of  blood,  244 

of  tissues,  245 
Urine  in  scurvy,  204-206 


Vegetable  juices,  keeping  qualities  of, 

161 
Vegetables,    antiscorbutic    value    of 
144,  158 
canned,  166 
dehydrated,  163 
effect  of  heat  on,  159 
fresh,  144,  158 

ripeness  of,   effect  on   antiscor- 
butic value,  160 
Vitamine,  antiscorbutic,  general  dis- 
cussion of,  62 
action  of,  68,  69 
as  antitoxin,  69 
as  catalytic  agent,  70 
as  nutriment,  69 
blood  content  of,  76 
effect  of  heat  on,  65 

of  ultra-violet  ray  on,  67 
excretion  of,  77 


INDEX 


279 


Vitamine,  experimental  evidence  for, 
62 

fate  in  body,  74,  77 

relation   to   water-soluble 
factor,  65,  67 

relation  to  antineuritic  vita- 
mine,  67 

resistance  to  chemical  and 
physical  processes,  64 

storage  in  body  of,  74 
theory  of  scurvy,  32 


W 

Weight,  loss  of,  138,  213 

"White  line"  of  Fraenkel,  128,  198 

World  War,  scurvy  in,  15 

X 

X-ray  in  diagnosis  of  scurvy,  128,  192, 
198 


Yeast,  antiscorbutic  value  of,  171 


Date  Due 

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